15-44711587-C-T

Variant names:

• chr15-44711587-C-T
• rs986783978
• NM_004048.4:c.41C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004048.4(B2M):​c.41C>T​(p.Ser14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: B2M NM_004048.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05172482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B2M	NM_004048.4	c.41C>T	p.Ser14Phe	missense_variant	Exon 1 of 4	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.41C>T	p.Ser14Phe	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.41C>T	p.Ser14Phe	missense_variant	Exon 1 of 4		NM_004048.4	ENSP00000497910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.92
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.085	N
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	.;L;L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.19	N;N;N;.
REVEL	Benign	0.013
Sift	Benign	0.67	T;T;T;.
Sift4G	Benign	0.73	T;T;T;.
Polyphen		0.0010	B;B;B;B
Vest4		0.20
MutPred		0.50		Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.29
MPC		1.1
ClinPred		0.13	T
GERP RS		-3.7
Varity_R		0.051
gMVP		0.54

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: rs986783978; hg19: chr15-45003785;