Genetic Variant BSG:p.Leu240Leu (chr19-580710-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001728.4(BSG):c.720G>A(p.Leu240Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,592,250 control chromosomes in the GnomAD database, including 847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.023 ( 62 hom., cov: 33)

Exomes 𝑓: 0.024 ( 785 hom. )

Consequence

BSG
NM_001728.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.04

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-580710-G-A is Benign according to our data. Variant chr19-580710-G-A is described in ClinVar as [Benign]. Clinvar id is 3037529.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.04 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0232 (3521/152068) while in subpopulation NFE AF= 0.0366 (2481/67856). AF 95% confidence interval is 0.0354. There are 62 homozygotes in gnomad4. There are 1654 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 62 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSG	NM_001728.4 link	c.720G>A	p.Leu240Leu	synonymous_variant	Exon 5 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.720G>A	p.Leu240Leu	synonymous_variant	Exon 5 of 9	1	NM_001728.4	ENSP00000333769.3		P35613-1

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3521

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0366

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0241

AC:

6034

AN:

250106

Hom.:

108

AF XY:

0.0249

AC XY:

3372

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00415

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0243

AC:

34955

AN:

1440182

Hom.:

785

Cov.:

AF XY:

0.0240

AC XY:

17221

AN XY:

716816

show subpopulations

Gnomad4 AFR exome

AF:

0.00437

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00786

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0279

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0232

AC:

3521

AN:

152068

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1654

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.0255

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.0185

Gnomad4 NFE

AF:

0.0366

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0309

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BSG-related disorder

Benign:1

Feb 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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