1-151365227-C-T

Position:

• chr1-151365227-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003944.4(SELENBP1):​c.1099G>A​(p.Glu367Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,590 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (14 hom., cov: 32)
  • Exomes 𝑓: 0.011 (129 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027176738).
• BP6: Variant 1-151365227-C-T is Benign according to our data. Variant chr1-151365227-C-T is described in ClinVar as [Benign]. Clinvar id is 775140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-151365227-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0114 (16709/1461342) while in subpopulation MID AF= 0.0193 (111/5764). AF 95% confidence interval is 0.0164. There are 129 homozygotes in gnomad4_exome. There are 8146 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENBP1	NM_003944.4	c.1099G>A	p.Glu367Lys	missense_variant	10/12	ENST00000368868.10
SELENBP1	NM_001258289.2	c.1225G>A	p.Glu409Lys	missense_variant	10/12
SELENBP1	NM_001258288.2	c.913G>A	p.Glu305Lys	missense_variant	9/11
SELENBP1	XM_047433576.1	c.*92G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENBP1	ENST00000368868.10	c.1099G>A	p.Glu367Lys	missense_variant	10/12	1	NM_003944.4	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1760 AN: 152130 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00930 AC: 2323 AN: 249836 Hom.: 19 AF XY: 0.00890 AC XY: 1202 AN XY: 135038

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.00874

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00585

Gnomad FIN exome AF: 0.000931

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.0114 AC: 16709 AN: 1461342 Hom.: 129 Cov.: 31 AF XY: 0.0112 AC XY: 8146 AN XY: 726956

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.00893

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00639

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0116 AC: 1761 AN: 152248 Hom.: 14 Cov.: 32 AF XY: 0.00997 AC XY: 742 AN XY: 74426

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0117 Hom.: 20

Bravo AF: 0.0128

TwinsUK AF: 0.0135 AC: 50

ALSPAC AF: 0.0166 AC: 64

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.0121 AC: 104

ExAC AF: 0.00915 AC: 1111

Asia WGS AF: 0.00173 AC: 7 AN: 3478

EpiCase AF: 0.0137

EpiControl AF: 0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.014	T;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	T;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.035	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.47	N;N;.
REVEL	Benign	0.046
Sift	Benign	0.67	T;T;.
Sift4G	Benign	0.73	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.16
MVP		0.076
MPC		0.098
ClinPred		0.0074	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.37

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: rs72710112; hg19: chr1-151337703; COSMIC: COSV64374302; COSMIC: COSV64374302;