rs7006628

Variant names:

• chr8-10187603-G-A
• rs7006628
• NM_012331.5:c.143-20230G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-10187603-G-A
• chr8-10187603-G-C

Variant summary

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

The NM_012331.5(MSRA):​c.143-20230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,046 control chromosomes in the GnomAD database, including 15,188 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 0.45 (15188 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-20230G>A		intron_variant	Intron 1 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.143-20230G>A		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67717 AN: 151928 Hom.: 15162 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.446 AC: 67801 AN: 152046 Hom.: 15188 Cov.: 32 AF XY: 0.447 AC XY: 33185 AN XY: 74316

African (AFR) AF: 0.456 AC: 18908 AN: 41452

American (AMR) AF: 0.429 AC: 6550 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2540 AN: 5166

South Asian (SAS) AF: 0.590 AC: 2841 AN: 4818

European-Finnish (FIN) AF: 0.409 AC: 4320 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29666 AN: 67978

Other (OTH) AF: 0.433 AC: 914 AN: 2110

Alfa AF: 0.445 Hom.: 8830

Bravo AF: 0.450

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7006628; hg19: chr8-10045113;