chr16-1940993-T-C

Variant names:

• chr16-1940993-T-C
• rs13331553
• NM_016332.4:c.205-101A>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.205-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,573,354 control chromosomes in the GnomAD database, including 84,339 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 0.37 (11659 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72680 hom.)
• Consequence: MSRB1 NM_016332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 14 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 (MetaRNN=2.6244059E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 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.205-101A>G		intron	N/A	NP_057416.1
	MSRB1	NM_001382264.1		c.173-101A>G		intron	N/A	NP_001369193.1
	MSRB1	NM_001382265.1		c.204+264A>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.205-101A>G		intron	N/A	ENSP00000355084.3
	MSRB1	ENST00000399753.3		n.507A>G		non_coding_transcript_exon	Exon 2 of 3
	MSRB1	ENST00000489198.1	TSL:3	n.694A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56125 AN: 151902 Hom.: 11641 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.335 AC: 61708 AN: 184176 AF XY: 0.345

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.531

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.308 AC: 438401 AN: 1421332 Hom.: 72680 Cov.: 78 AF XY: 0.314 AC XY: 220787 AN XY: 703562

African (AFR) AF: 0.563 AC: 18246 AN: 32402

American (AMR) AF: 0.178 AC: 6728 AN: 37748

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9546 AN: 25364

East Asian (EAS) AF: 0.581 AC: 21666 AN: 37278

South Asian (SAS) AF: 0.478 AC: 39354 AN: 82320

European-Finnish (FIN) AF: 0.277 AC: 13906 AN: 50258

Middle Eastern (MID) AF: 0.296 AC: 1695 AN: 5718

European-Non Finnish (NFE) AF: 0.282 AC: 307835 AN: 1091242

Other (OTH) AF: 0.329 AC: 19425 AN: 59002

GnomAD4 genome AF: 0.370 AC: 56189 AN: 152022 Hom.: 11659 Cov.: 32 AF XY: 0.369 AC XY: 27407 AN XY: 74284

African (AFR) AF: 0.548 AC: 22732 AN: 41466

American (AMR) AF: 0.244 AC: 3729 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2737 AN: 5126

South Asian (SAS) AF: 0.481 AC: 2318 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2921 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19323 AN: 67960

Other (OTH) AF: 0.350 AC: 738 AN: 2110

Alfa AF: 0.310 Hom.: 23666

Bravo AF: 0.370

TwinsUK AF: 0.284 AC: 1053

ALSPAC AF: 0.271 AC: 1043

ExAC AF: 0.305 AC: 34978

Asia WGS AF: 0.469 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.7
DANN	Benign	0.40
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.000026	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.23
PROVEAN	Benign	0.0	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Vest4		0.051
ClinPred		0.012	T
GERP RS		-2.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs13331553; hg19: chr16-1990994; COSMIC: COSV51907767; COSMIC: COSV51907767;