15-44713183-T-C

Variant names:

• chr15-44713183-T-C
• rs1901531
• NM_004048.4:c.67+1570T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

B2M Gene-Disease associations (from GenCC):

• hypoproteinemia, hypercatabolic

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• variant ABeta2M amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• MHC class I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial visceral amyloidosis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004048.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B2M	NM_004048.4	MANE Select	c.67+1570T>C		intron	N/A	NP_004039.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B2M	ENST00000648006.3	MANE Select	c.67+1570T>C		intron	N/A	ENSP00000497910.1
	B2M	ENST00000559916.1	TSL:1	c.67+1570T>C		intron	N/A	ENSP00000453350.1
	B2M	ENST00000557901.5	TSL:1	n.67+1570T>C		intron	N/A	ENSP00000452861.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0350 AC: 1454 AN: 41528

American (AMR) AF: 0.131 AC: 2006 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0644 AC: 310 AN: 4812

European-Finnish (FIN) AF: 0.214 AC: 2259 AN: 10562

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12821 AN: 67970

Other (OTH) AF: 0.144 AC: 304 AN: 2106

Alfa AF: 0.171 Hom.: 5212

Bravo AF: 0.119

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs1901531; hg19: chr15-45005381;