rs2296467

Positions:

• chr10-23104339-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012228.4(MSRB2):​c.219+95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 912,040 control chromosomes in the GnomAD database, including 24,550 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 0.19 (3156 hom., cov: 31)
  • Exomes 𝑓: 0.23 (21394 hom.)
• Consequence: MSRB2 NM_012228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB2	NM_012228.4	c.219+95A>T		intron_variant		ENST00000376510.8	NP_036360.3
MSRB2	XM_011519426.3	c.219+95A>T		intron_variant			XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB2	ENST00000376510.8	c.219+95A>T		intron_variant		1	NM_012228.4	ENSP00000365693	P1
	ENST00000655462.1	n.116+29350T>A		intron_variant, non_coding_transcript_variant
MSRB2	ENST00000472663.1	c.101+95A>T		intron_variant, NMD_transcript_variant		5		ENSP00000434990

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28153 AN: 151776 Hom.: 3157 Cov.: 31

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.234 AC: 178106 AN: 760146 Hom.: 21394 AF XY: 0.236 AC XY: 92334 AN XY: 391758

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.185 AC: 28159 AN: 151894 Hom.: 3156 Cov.: 31 AF XY: 0.190 AC XY: 14073 AN XY: 74216

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.206

Alfa AF: 0.214 Hom.: 495

Bravo AF: 0.168

Asia WGS AF: 0.293 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.63

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: rs2296467; hg19: chr10-23393268;