chr8-10214110-A-G

Variant names:

• chr8-10214110-A-G
• rs11775334
• NM_012331.5:c.211+6209A>G

Variant summary

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

The NM_012331.5(MSRA):​c.211+6209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,994 control chromosomes in the GnomAD database, including 25,517 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 0.57 (25517 hom., cov: 31)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 24 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.211+6209A>G		intron_variant	Intron 2 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.211+6209A>G		intron_variant	Intron 2 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86240 AN: 151876 Hom.: 25502 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.568 AC: 86286 AN: 151994 Hom.: 25517 Cov.: 31 AF XY: 0.567 AC XY: 42119 AN XY: 74270

African (AFR) AF: 0.391 AC: 16228 AN: 41464

American (AMR) AF: 0.588 AC: 8987 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2323 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2368 AN: 5142

South Asian (SAS) AF: 0.559 AC: 2695 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6522 AN: 10546

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45168 AN: 67958

Other (OTH) AF: 0.591 AC: 1249 AN: 2112

Alfa AF: 0.631 Hom.: 133009

Bravo AF: 0.555

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.47
PhyloP100		-0.64
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: rs11775334; hg19: chr8-10071620;