19-572645-C-G

Variant names:

• chr19-572645-C-G
• rs772237058
• NM_001728.4:c.11C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001728.4(BSG):​c.11C>G​(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,352,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000022 (0 hom.)
• Consequence: BSG NM_001728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.62
• Publications: 0 publications found

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-AS1 (HGNC:55286): (BSG antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20147955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSG	NM_001728.4	MANE Select	c.11C>G	p.Ala4Gly	missense	Exon 1 of 9	NP_001719.2
	BSG	NM_001322243.2		c.11C>G	p.Ala4Gly	missense	Exon 1 of 8	NP_001309172.1	P35613-2
	BSG	NM_198589.3		c.11C>G	p.Ala4Gly	missense	Exon 1 of 8	NP_940991.1	P35613-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSG	ENST00000333511.9	TSL:1 MANE Select	c.11C>G	p.Ala4Gly	missense	Exon 1 of 9	ENSP00000333769.3	P35613-1
	BSG	ENST00000353555.9	TSL:1	c.11C>G	p.Ala4Gly	missense	Exon 1 of 8	ENSP00000343809.4	P35613-2
	BSG	ENST00000346916.9	TSL:1	c.-56+1066C>G		intron	N/A	ENSP00000344707.4	P35613-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1352462 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 668586

African (AFR) AF: 0.00 AC: 0 AN: 27862

American (AMR) AF: 0.00 AC: 0 AN: 30342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23620

East Asian (EAS) AF: 0.00 AC: 0 AN: 29990

South Asian (SAS) AF: 0.00 AC: 0 AN: 74590

European-Finnish (FIN) AF: 0.0000210 AC: 1 AN: 47660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1057296

Other (OTH) AF: 0.00 AC: 0 AN: 55546

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.084
DANN	Benign	0.58
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.068
Sift	Benign	0.32	T
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.73		Loss of helix (P = 0.0068)
MVP		0.22
MPC		0.15
ClinPred		0.086	T
GERP RS		-4.3
PromoterAI		-0.10	Neutral
Varity_R		0.067
gMVP		0.35
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772237058; hg19: chr19-572645;