chr1-151364974-G-A

Position:

• chr1-151364974-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_003944.4(SELENBP1):​c.1208C>T​(p.Thr403Met) variant causes a missense change. The variant allele was found at a frequency of 0.00237 in 1,613,852 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T403K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0014 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (115 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.25

Genes affected

SELENBP1 (HGNC:10719): (selenium binding protein 1) This gene encodes a member of the selenium-binding protein family. Selenium is an essential nutrient that exhibits potent anticarcinogenic properties, and deficiency of selenium may cause certain neurologic diseases. The effects of selenium in preventing cancer and neurologic diseases may be mediated by selenium-binding proteins, and decreased expression of this gene may be associated with several types of cancer. The encoded protein may play a selenium-dependent role in ubiquitination/deubiquitination-mediated protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014660746).
• BP6: Variant 1-151364974-G-A is Benign according to our data. Variant chr1-151364974-G-A is described in ClinVar as [Benign]. Clinvar id is 3037494.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00137 (208/152220) while in subpopulation SAS AF= 0.0407 (196/4820). AF 95% confidence interval is 0.036. There are 8 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENBP1	NM_003944.4	c.1208C>T	p.Thr403Met	missense_variant	11/12	ENST00000368868.10
SELENBP1	NM_001258289.2	c.1334C>T	p.Thr445Met	missense_variant	11/12
SELENBP1	NM_001258288.2	c.1022C>T	p.Thr341Met	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENBP1	ENST00000368868.10	c.1208C>T	p.Thr403Met	missense_variant	11/12	1	NM_003944.4	P1

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 209 AN: 152102 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.00503 AC: 1257 AN: 250120 Hom.: 39 AF XY: 0.00680 AC XY: 919 AN XY: 135108

Gnomad AFR exome AF: 0.000372

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.0402

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00248 AC: 3622 AN: 1461632 Hom.: 115 Cov.: 31 AF XY: 0.00355 AC XY: 2579 AN XY: 727090

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000450

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152220 Hom.: 8 Cov.: 32 AF XY: 0.00214 AC XY: 159 AN XY: 74434

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0407

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000235 Hom.: 0

Bravo AF: 0.000317

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00574 AC: 697

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELENBP1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;D
MetaRNN	Benign	0.015	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.0	D;D;.
REVEL	Benign	0.27
Sift	Uncertain	0.015	D;D;.
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.82	P;.;.
Vest4		0.79
MVP		0.38
MPC		0.37
ClinPred		0.043	T
GERP RS		4.3
Varity_R		0.15
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201363174; hg19: chr1-151337450; COSMIC: COSV64373634; COSMIC: COSV64373634;