rs4840463

chr8-10100811-A-C

Variant summary

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

The NM_012331.5(MSRA):c.142+46153A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,852 control chromosomes in the GnomAD database, including 29,104 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 0.60 (29104 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5	c.142+46153A>C		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.142+46153A>C		intron_variant		1	NM_012331.5	P1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91589 AN: 151734 Hom.: 29120 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.603 AC: 91579 AN: 151852 Hom.: 29104 Cov.: 31 AF XY: 0.603 AC XY: 44710 AN XY: 74190

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.646

Alfa AF: 0.674 Hom.: 18702

Bravo AF: 0.590

Asia WGS AF: 0.533 AC: 1853 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	0.43
Dann	Benign	0.70

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: rs4840463; hg19: chr8-9958321;