Variant 20-50841890-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198799.4(BCAS4):c.389C>A(p.Ser130Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,584,220 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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. S130T) 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, single submitter B:1

Conservation

PhyloP100: 1.04

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004421115).

BP6

Variant 20-50841890-C-A is Benign according to our data. Variant chr20-50841890-C-A is described in ClinVar as [Benign]. Clinvar id is 713433.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00863 (1314/152280) while in subpopulation AFR AF= 0.0295 (1225/41556). AF 95% confidence interval is 0.0281. 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 GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAS4	NM_198799.4 linkuse as main transcript	c.389C>A	p.Ser130Tyr	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.389C>A	p.Ser130Tyr	missense_variant	4/5	1	NM_198799.4	P2

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

1308

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

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:

0.00430

GnomAD3 exomes

AF:

0.00240

AC:

547

AN:

227670

Hom.:

AF XY:

0.00181

AC XY:

224

AN XY:

123522

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000738

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.000960

AC:

1374

AN:

1431940

Hom.:

Cov.:

AF XY:

0.000849

AC XY:

602

AN XY:

709362

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000961

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00241

GnomAD4 genome

AF:

0.00863

AC:

1314

AN:

152280

Hom.:

Cov.:

AF XY:

0.00804

AC XY:

599

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0295

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:

0.00425

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00936

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00267

AC:

324

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

D;D;.

REVEL

Benign

0.045

Sift

Uncertain

0.0020

D;D;.

Sift4G

Benign

0.12

T;D;T

Polyphen

0.99

D;D;.

Vest4

0.28

MVP

0.49

MPC

0.93

ClinPred

0.023

GERP RS

2.4

Varity_R

0.15

gMVP

0.37

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