16-1941512-G-C

Variant names:

• chr16-1941512-G-C
• rs9934331
• NM_016332.4:c.56-107C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016332.4. 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
	MSRB1	NM_016332.4	MANE Select	c.56-107C>G		intron	N/A	NP_057416.1
	MSRB1	NM_001382264.1		c.56-107C>G		intron	N/A	NP_001369193.1
	MSRB1	NM_001382265.1		c.56-107C>G		intron	N/A	NP_001369194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRB1	ENST00000361871.8	TSL:1 MANE Select	c.56-107C>G		intron	N/A	ENSP00000355084.3
	MSRB1	ENST00000564908.1	TSL:3	c.56-107C>G		intron	N/A	ENSP00000456557.1
	MSRB1	ENST00000473663.1	TSL:5	c.22-107C>G		intron	N/A	ENSP00000457320.1

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

African (AFR) AF: 0.120 AC: 3385 AN: 28162

American (AMR) AF: 0.118 AC: 2943 AN: 24922

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4621 AN: 19770

East Asian (EAS) AF: 0.475 AC: 16611 AN: 34948

South Asian (SAS) AF: 0.366 AC: 24210 AN: 66194

European-Finnish (FIN) AF: 0.144 AC: 5905 AN: 41122

Middle Eastern (MID) AF: 0.227 AC: 882 AN: 3880

European-Non Finnish (NFE) AF: 0.175 AC: 176516 AN: 1010890

Other (OTH) AF: 0.209 AC: 11132 AN: 53230

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

African (AFR) AF: 0.121 AC: 5006 AN: 41524

American (AMR) AF: 0.147 AC: 2248 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2326 AN: 5114

South Asian (SAS) AF: 0.372 AC: 1795 AN: 4820

European-Finnish (FIN) AF: 0.146 AC: 1550 AN: 10596

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.177 AC: 12027 AN: 67998

Other (OTH) AF: 0.188 AC: 398 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		-0.35
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: rs9934331; hg19: chr16-1991513;