15-44711551-C-G

Position:

• chr15-44711551-C-G

Variant summary

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

The NM_004048.4(B2M):​c.5C>G​(p.Ser2Cys) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B2M NM_004048.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567

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 (HGNC:):

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=0.26173413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B2M	NM_004048.4	c.5C>G	p.Ser2Cys	missense_variant	1/4	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.5C>G	p.Ser2Cys	missense_variant	1/2		XP_005254606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.5C>G	p.Ser2Cys	missense_variant	1/4		NM_004048.4	ENSP00000497910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T;T;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.1	.;L;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N;N;N;.
REVEL	Benign	0.086
Sift	Uncertain	0.010	D;D;D;.
Sift4G	Uncertain	0.0080	D;D;D;.
Polyphen		0.96	D;P;P;P
Vest4		0.24
MutPred		0.34		Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);
MVP		0.48
MPC		0.95
ClinPred		0.30	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.56

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: rs368160918; hg19: chr15-45003749;