rs6983870

Variant names:

• chr8-10253784-G-A
• rs6983870
• NM_012331.5:c.331+8561G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-10253784-G-A
• chr8-10253784-G-T

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+8561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,914 control chromosomes in the GnomAD database, including 7,782 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 0.30 (7782 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 3 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	NM_012331.5	MANE Select	c.331+8561G>A		intron	N/A	NP_036463.1
	MSRA	NM_001135670.3		c.211+45883G>A		intron	N/A	NP_001129142.1
	MSRA	NM_001135671.3		c.202+8561G>A		intron	N/A	NP_001129143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRA	ENST00000317173.9	TSL:1 MANE Select	c.331+8561G>A		intron	N/A	ENSP00000313921.4
	MSRA	ENST00000382490.9	TSL:1	c.202+8561G>A		intron	N/A	ENSP00000371930.5
	MSRA	ENST00000528246.5	TSL:1	c.133+8561G>A		intron	N/A	ENSP00000436839.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46299 AN: 151796 Hom.: 7776 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.305 AC: 46330 AN: 151914 Hom.: 7782 Cov.: 32 AF XY: 0.294 AC XY: 21792 AN XY: 74208

African (AFR) AF: 0.248 AC: 10279 AN: 41400

American (AMR) AF: 0.255 AC: 3890 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.113 AC: 543 AN: 4812

European-Finnish (FIN) AF: 0.276 AC: 2894 AN: 10500

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26007 AN: 67964

Other (OTH) AF: 0.350 AC: 735 AN: 2102

Alfa AF: 0.348 Hom.: 1531

Bravo AF: 0.301

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.2
DANN	Benign	0.46
PhyloP100		-0.15
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: rs6983870; hg19: chr8-10111294;