Genetic Variant NM_198799.4:c.350A>G (chr20-50841851-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198799.4(BCAS4):c.350A>G(p.Gln117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

BCAS4
NM_198799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03388107).

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.350A>G	p.Gln117Arg	missense	Exon 4 of 5	NP_942094.3	A0A804CEY2
BCAS4	NM_017843.4		c.440A>G	p.Gln147Arg	missense	Exon 4 of 6	NP_060313.3	Q8TDM0-1
BCAS4	NM_001010974.2		c.354+11471A>G		intron	N/A	NP_001010974.1	Q8TDM0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAS4	ENST00000371608.8	TSL:1 MANE Select	c.350A>G	p.Gln117Arg	missense	Exon 4 of 5	ENSP00000360669.3	A0A804CEY2
BCAS4	ENST00000358791.9	TSL:1	c.440A>G	p.Gln147Arg	missense	Exon 4 of 6	ENSP00000351642.5	Q8TDM0-1
BCAS4	ENST00000609336.5	TSL:1	c.350A>G	p.Gln117Arg	missense	Exon 4 of 6	ENSP00000477167.1	A0A0C4DGS6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248544

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459304

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.0000900

AC:

AN:

44466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110652

Other (OTH)

AF:

0.00

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.0

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.48

M_CAP

Benign

0.0064

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.52

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.51

REVEL

Benign

0.014

Sift

Benign

0.47

Sift4G

Benign

0.62

Polyphen

0.0020

Vest4

0.080

MutPred

0.35

Gain of MoRF binding (P = 0.0147)

MVP

0.095

MPC

0.27

ClinPred

0.022

GERP RS

-1.6

Varity_R

0.024

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over