15-44711572-T-C

Position:

• chr15-44711572-T-C

Variant summary

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

The NM_004048.4(B2M):​c.26T>C​(p.Val9Ala) 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. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: B2M NM_004048.4 missense
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 1.60

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=0.094842166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B2M	NM_004048.4	c.26T>C	p.Val9Ala	missense_variant	1/4	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.26T>C	p.Val9Ala	missense_variant	1/2		XP_005254606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.26T>C	p.Val9Ala	missense_variant	1/4		NM_004048.4	ENSP00000497910	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.038	T;T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	.;N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Benign	0.078
Sift	Benign	0.11	T;T;T;.
Sift4G	Uncertain	0.024	D;T;T;.
Polyphen		0.038	B;B;B;B
Vest4		0.23
MutPred		0.47		Gain of disorder (P = 0.0547);Gain of disorder (P = 0.0547);Gain of disorder (P = 0.0547);Gain of disorder (P = 0.0547);
MVP		0.26
MPC		0.88
ClinPred		0.17	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45003770;