10-23111262-T-C

Variant names:

• chr10-23111262-T-C
• rs11013291
• NM_012228.4:c.296+944T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012228.4(MSRB2):​c.296+944T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,082 control chromosomes in the GnomAD database, including 12,295 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 0.39 (12295 hom., cov: 32)
• Consequence: MSRB2 NM_012228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 2 publications found

Genes affected

MSRB2 (HGNC:17061): (methionine sulfoxide reductase B2) Predicted to enable actin binding activity; peptide-methionine (R)-S-oxide reductase activity; and zinc ion binding activity. Predicted to be involved in actin filament polymerization and protein repair. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286924 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB2	NM_012228.4	c.296+944T>C		intron_variant	Intron 3 of 4	ENST00000376510.8	NP_036360.3
MSRB2	XM_011519426.3	c.296+944T>C		intron_variant	Intron 3 of 3		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRB2	ENST00000376510.8	c.296+944T>C		intron_variant	Intron 3 of 4	1	NM_012228.4	ENSP00000365693.3
MSRB2	ENST00000472663.1	n.176+944T>C		intron_variant	Intron 2 of 4	5		ENSP00000434990.1
ENSG00000286924	ENST00000655462.1	n.116+22427A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59618 AN: 151964 Hom.: 12293 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59624 AN: 152082 Hom.: 12295 Cov.: 32 AF XY: 0.388 AC XY: 28847 AN XY: 74344

African (AFR) AF: 0.311 AC: 12910 AN: 41498

American (AMR) AF: 0.296 AC: 4525 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1402 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1544 AN: 5150

South Asian (SAS) AF: 0.376 AC: 1816 AN: 4826

European-Finnish (FIN) AF: 0.431 AC: 4556 AN: 10566

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31630 AN: 67974

Other (OTH) AF: 0.367 AC: 777 AN: 2116

Alfa AF: 0.430 Hom.: 47026

Bravo AF: 0.377

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.3
DANN	Benign	0.75
PhyloP100		-0.095
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: rs11013291; hg19: chr10-23400191;