rs1901531

Positions:

• chr15-44713183-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004048.4(B2M):​c.67+1570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,110 control chromosomes in the GnomAD database, including 1,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1753 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: B2M NM_004048.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B2M	NM_004048.4	c.67+1570T>C		intron_variant		ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.67+1570T>C		intron_variant			XP_005254606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.67+1570T>C		intron_variant			NM_004048.4	ENSP00000497910	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19847 AN: 151986 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 SAS exome AF: 0.167

GnomAD4 genome AF: 0.130 AC: 19844 AN: 152104 Hom.: 1753 Cov.: 32 AF XY: 0.130 AC XY: 9679 AN XY: 74344

Gnomad4 AFR AF: 0.0350

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.144

Alfa AF: 0.174 Hom.: 3788

Bravo AF: 0.119

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.30

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: rs1901531; hg19: chr15-45005381;