rs1484645

chr8-10143456-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MSRA	NM_012331.5	c.143-64377A>G		intron_variant		ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9	c.143-64377A>G		intron_variant		1	NM_012331.5	P1
	ENST00000649481.2	n.514+3509T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0647

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.206

Alfa AF: 0.212 Hom.: 7823

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1484645; hg19: chr8-10000966;