rs765817584

Variant names:

• chr15-44711553-C-A
• rs765817584
• NM_004048.4:c.7C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-44711553-C-A
• chr15-44711553-C-G
• chr15-44711553-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004048.4(B2M):​c.7C>A​(p.Arg3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B2M NM_004048.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

B2M (HGNC:914): (beta-2-microglobulin) This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079919815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B2M	NM_004048.4	c.7C>A	p.Arg3Ser	missense_variant	Exon 1 of 4	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.7C>A	p.Arg3Ser	missense_variant	Exon 1 of 2		XP_005254606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.7C>A	p.Arg3Ser	missense_variant	Exon 1 of 4		NM_004048.4	ENSP00000497910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461576 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	.;L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Benign	0.011
Sift	Benign	0.22	T;T;T;.
Sift4G	Benign	0.39	T;T;T;.
Polyphen		0.032	B;B;B;B
Vest4		0.18
MutPred		0.47		Loss of MoRF binding (P = 0.0201);Loss of MoRF binding (P = 0.0201);Loss of MoRF binding (P = 0.0201);Loss of MoRF binding (P = 0.0201);
MVP		0.29
MPC		1.9
ClinPred		0.40	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.084
gMVP		0.57

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

Other links and lift over

dbSNP: rs765817584; hg19: chr15-45003751; COSMIC: COSV105270900; COSMIC: COSV105270900;