rs139940313

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_198799.4(BCAS4):c.425C>T(p.Thr142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,946 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

BCAS4
NM_198799.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.474

Publications

3 publications found

Variant links:

Genes affected

BCAS4 (HGNC:14367): (breast carcinoma amplified sequence 4) Predicted to be part of BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

BCAS4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022736907).

BP6

Variant 20-50876511-C-T is Benign according to our data. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-50876511-C-T is described in CliVar as Likely_benign. Clinvar id is 781500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS4	NM_198799.4 link	c.425C>T	p.Thr142Met	missense_variant	Exon 5 of 5	ENST00000371608.8	NP_942094.3	Q8TDM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS4	ENST00000371608.8 link	c.425C>T	p.Thr142Met	missense_variant	Exon 5 of 5	1	NM_198799.4	ENSP00000360669.3		A0A804CEY2

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000539

AC:

135

AN:

250610

AF XY:

0.000495

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00121

AC:

1765

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

829

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00149

AC:

1660

AN:

1111894

Other (OTH)

AF:

0.00151

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

181

271

362

452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000545

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41564

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000830

Hom.:

Bravo

AF:

0.000589

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000486

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Sep 14, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.8

(source)

DANN

Benign

0.80

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.47

PROVEAN

Benign

-0.58

N;.

REVEL

Benign

0.013

Sift

Benign

0.17

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.11

B;.

Vest4

0.092

MVP

0.20

ClinPred

0.0044

GERP RS

-0.086

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over