19-572645-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001728.4(BSG):​c.11C>A​(p.Ala4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000399 in 1,504,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A4G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BSG NM_001728.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30854803).

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>A	p.Ala4Glu	missense	Exon 1 of 9	NP_001719.2
	BSG	NM_001322243.2		c.11C>A	p.Ala4Glu	missense	Exon 1 of 8	NP_001309172.1	P35613-2
	BSG	NM_198589.3		c.11C>A	p.Ala4Glu	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>A	p.Ala4Glu	missense	Exon 1 of 9	ENSP00000333769.3	P35613-1
	BSG	ENST00000353555.9	TSL:1	c.11C>A	p.Ala4Glu	missense	Exon 1 of 8	ENSP00000343809.4	P35613-2
	BSG	ENST00000346916.9	TSL:1	c.-56+1066C>A		intron	N/A	ENSP00000344707.4	P35613-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1352462 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 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: 0.0000134 AC: 1 AN: 74590

European-Finnish (FIN) AF: 0.00 AC: 0 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 AF: 0.0000197 AC: 3 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74300

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.036
DANN	Benign	0.72
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Uncertain	0.032	D
Polyphen		0.11	B
Vest4		0.25
MutPred		0.77		Loss of helix (P = 0.0104)
MVP		0.20
MPC		0.18
ClinPred		0.15	T
GERP RS		-4.3
PromoterAI		-0.065	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.12
gMVP		0.52
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs772237058; hg19: chr19-572645;