rs7001821

Variant names:

• chr8-10272263-T-C
• rs7001821
• NM_012331.5:c.331+27040T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-10272263-T-C
• chr8-10272263-T-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.331+27040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,908 control chromosomes in the GnomAD database, including 22,990 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 0.55 (22990 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.331+27040T>C		intron	N/A	NP_036463.1	Q9UJ68-1
	MSRA	NM_001135670.3		c.212-29271T>C		intron	N/A	NP_001129142.1	Q9UJ68-4
	MSRA	NM_001135671.3		c.202+27040T>C		intron	N/A	NP_001129143.1	Q9UJ68-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.331+27040T>C		intron	N/A	ENSP00000313921.4	Q9UJ68-1
	MSRA	ENST00000382490.9	TSL:1	c.202+27040T>C		intron	N/A	ENSP00000371930.5	Q9UJ68-3
	MSRA	ENST00000528246.5	TSL:1	c.133+27040T>C		intron	N/A	ENSP00000436839.1	Q9UJ68-2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82884 AN: 151790 Hom.: 22971 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.546 AC: 82947 AN: 151908 Hom.: 22990 Cov.: 33 AF XY: 0.541 AC XY: 40203 AN XY: 74256

African (AFR) AF: 0.451 AC: 18673 AN: 41436

American (AMR) AF: 0.518 AC: 7919 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2265 AN: 5158

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4820

European-Finnish (FIN) AF: 0.598 AC: 6294 AN: 10520

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.614 AC: 41681 AN: 67926

Other (OTH) AF: 0.577 AC: 1216 AN: 2108

Alfa AF: 0.588 Hom.: 111689

Bravo AF: 0.536

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.73
PhyloP100		-0.058
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: rs7001821; hg19: chr8-10129773;