Genetic Variant BCAS4:p.Pro25Pro (chr20-50795158-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_198799.4(BCAS4):c.75C>T(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,461,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000093 ( 1 hom. )

Consequence

BCAS4
NM_198799.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.065).

BP6

Variant 20-50795158-C-T is Benign according to our data. Variant chr20-50795158-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 748265.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.98 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198799.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAS4	NM_198799.4	MANE Select	c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 5	NP_942094.3	A0A804CEY2
BCAS4	NM_017843.4		c.165C>T	p.Pro55Pro	synonymous	Exon 1 of 6	NP_060313.3	Q8TDM0-1
BCAS4	NM_001010974.2		c.165C>T	p.Pro55Pro	synonymous	Exon 1 of 4	NP_001010974.1	Q8TDM0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAS4	ENST00000371608.8	TSL:1 MANE Select	c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 5	ENSP00000360669.3	A0A804CEY2
BCAS4	ENST00000358791.9	TSL:1	c.165C>T	p.Pro55Pro	synonymous	Exon 1 of 6	ENSP00000351642.5	Q8TDM0-1
BCAS4	ENST00000609336.5	TSL:1	c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 6	ENSP00000477167.1	A0A0C4DGS6

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000414

AC:

AN:

96678

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000551

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000932

AC:

122

AN:

1309480

Hom.:

Cov.:

AF XY:

0.0000929

AC XY:

AN XY:

645976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27452

American (AMR)

AF:

0.000131

AC:

AN:

30486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23008

East Asian (EAS)

AF:

0.00

AC:

AN:

29736

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34562

Middle Eastern (MID)

AF:

0.000193

AC:

AN:

5176

European-Non Finnish (NFE)

AF:

0.000110

AC:

114

AN:

1034502

Other (OTH)

AF:

0.0000372

AC:

AN:

53700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67992

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00

Hom.:

Bravo

AF:

0.0000567

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.9

(source)

DANN

Benign

0.95

PhyloP100

-3.0

PromoterAI

-0.019

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over