rs1484645

Variant names:

• chr8-10143456-A-G
• rs1484645
• NM_012331.5:c.143-64377A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012331.5(MSRA):​c.143-64377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,106 control chromosomes in the GnomAD database, including 4,313 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 0.20 (4313 hom., cov: 32)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 11 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]

ENSG00000285675 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.143-64377A>G		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.143-64377A>G		intron_variant	Intron 1 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31160 AN: 151990 Hom.: 4316 Cov.: 32

Gnomad AFR AF: 0.0648

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.205 AC: 31157 AN: 152106 Hom.: 4313 Cov.: 32 AF XY: 0.218 AC XY: 16238 AN XY: 74346

African (AFR) AF: 0.0647 AC: 2687 AN: 41526

American (AMR) AF: 0.326 AC: 4981 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2874 AN: 5156

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3667 AN: 10546

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14016 AN: 68002

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.206 Hom.: 11746

Bravo AF: 0.202

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		1.1
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: rs1484645; hg19: chr8-10000966;