Variant chr20-50841889-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198799.4(BCAS4):c.388T>A(p.Ser130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,585,184 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S130Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0086 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 7 hom. )

Consequence

BCAS4
NM_198799.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.48

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032875836).

BP6

Variant 20-50841889-T-A is Benign according to our data. Variant chr20-50841889-T-A is described in ClinVar as [Benign]. Clinvar id is 713432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00864 (1314/152046) while in subpopulation AFR AF= 0.0296 (1225/41446). AF 95% confidence interval is 0.0282. There are 17 homozygotes in gnomad4. There are 599 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAS4	NM_198799.4 linkuse as main transcript	c.388T>A	p.Ser130Thr	missense_variant	4/5	ENST00000371608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAS4	ENST00000371608.8 linkuse as main transcript	c.388T>A	p.Ser130Thr	missense_variant	4/5	1	NM_198799.4	P2

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

1308

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00238

AC:

545

AN:

229016

Hom.:

AF XY:

0.00179

AC XY:

223

AN XY:

124440

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00196

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000730

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.000956

AC:

1370

AN:

1433138

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

599

AN XY:

710166

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000958

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00241

GnomAD4 genome

AF:

0.00864

AC:

1314

AN:

152046

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

599

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00469

Hom.:

Bravo

AF:

0.00936

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00267

AC:

324

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.40

DANN

Benign

0.89

DEOGEN2

Benign

0.013

T;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.44

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.022

Sift

Benign

0.15

T;T;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.078

MVP

0.24

MPC

0.23

ClinPred

0.0012

GERP RS

-2.9

Varity_R

0.060

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over