chr16-1941512-G-C

Position:

• chr16-1941512-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016332.4(MSRB1):​c.56-107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,435,252 control chromosomes in the GnomAD database, including 29,601 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 0.17 (2687 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26914 hom.)
• Consequence: MSRB1 NM_016332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

Genes affected

MSRB1 (HGNC:14133): (methionine sulfoxide reductase B1) The protein encoded by this gene belongs to the methionine-R-sulfoxide reductase B (MsrB) family. Members of this family function as repair enzymes that protect proteins from oxidative stress by catalyzing the reduction of methionine-R-sulfoxides to methionines. This protein is highly expressed in liver and kidney, and is localized to the nucleus and cytosol. It is the only member of the MsrB family that is a selenoprotein, containing a selenocysteine (Sec) residue at its active site. It also has the highest methionine-R-sulfoxide reductase activity compared to other members containing cysteine in place of Sec. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A pseudogene of this locus has been identified on chromosome 19. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB1	NM_016332.4	c.56-107C>G		intron_variant		ENST00000361871.8
MSRB1	NM_001382264.1	c.56-107C>G		intron_variant
MSRB1	NM_001382265.1	c.56-107C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB1	ENST00000361871.8	c.56-107C>G		intron_variant		1	NM_016332.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26402 AN: 152016 Hom.: 2684 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.192 AC: 246205 AN: 1283118 Hom.: 26914 Cov.: 24 AF XY: 0.197 AC XY: 123632 AN XY: 626982

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.174 AC: 26425 AN: 152134 Hom.: 2687 Cov.: 32 AF XY: 0.178 AC XY: 13210 AN XY: 74372

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.188

Alfa AF: 0.174 Hom.: 299

Bravo AF: 0.168

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.50

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: rs9934331; hg19: chr16-1991513;