Genetic Variant NM_001728.4:c.842G>C (chr19-581364-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

-2

PM2BP4_Strong

The NM_001728.4(BSG):c.842G>C(p.Gly281Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,484 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G281V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BSG
NM_001728.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

1 publications found

Variant links:

Genes affected

BSG (HGNC:1116): (basigin (Ok blood group)) The protein encoded by this gene, basigin, is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. Basigin is also a member of the immunoglobulin superfamily, ubiquitously expressed in various tissues. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]

BSG 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=0.065651536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSG	NM_001728.4 link	c.842G>C	p.Gly281Ala	missense_variant	Exon 6 of 9	ENST00000333511.9	NP_001719.2	P35613-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSG	ENST00000333511.9 link	c.842G>C	p.Gly281Ala	missense_variant	Exon 6 of 9	1	NM_001728.4	ENSP00000333769.3		P35613-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248986

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460484

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.73

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.22

.;.;T;.;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.65

T;T;T;T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.066

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

.;.;N;.;.;.;.;.

PhyloP100

0.14

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.60

.;N;N;.;N;.;.;.

REVEL

Benign

0.13

Sift

Benign

0.30

.;T;T;.;T;.;.;.

Sift4G

Benign

0.31

T;T;T;T;T;T;T;T

Polyphen

0.018, 0.015

.;.;B;.;B;.;.;.

Vest4

0.073

MutPred

0.26

.;.;Gain of sheet (P = 0.0827);.;.;.;.;.;

MVP

0.25

MPC

0.16

ClinPred

0.022

GERP RS

-6.1

Varity_R

0.097

gMVP

0.48

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over