chr1-151365214-G-C

Position:

• chr1-151365214-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003944.4(SELENBP1):​c.1112C>G​(p.Ser371Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,884 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S371P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: SELENBP1 NM_003944.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.945

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0060944855).
• BP6: Variant 1-151365214-G-C is Benign according to our data. Variant chr1-151365214-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045077.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENBP1	NM_003944.4	c.1112C>G	p.Ser371Cys	missense_variant	10/12	ENST00000368868.10
SELENBP1	NM_001258289.2	c.1238C>G	p.Ser413Cys	missense_variant	10/12
SELENBP1	NM_001258288.2	c.926C>G	p.Ser309Cys	missense_variant	9/11
SELENBP1	XM_047433576.1	c.*105C>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENBP1	ENST00000368868.10	c.1112C>G	p.Ser371Cys	missense_variant	10/12	1	NM_003944.4	P1

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 152174 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00140 AC: 350 AN: 250424 Hom.: 1 AF XY: 0.00135 AC XY: 183 AN XY: 135366

Gnomad AFR exome AF: 0.000433

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.00248

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00162 AC: 2370 AN: 1461592 Hom.: 3 Cov.: 31 AF XY: 0.00152 AC XY: 1104 AN XY: 727072

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000828

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00206

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152292 Hom.: 2 Cov.: 32 AF XY: 0.00171 AC XY: 127 AN XY: 74444

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00188 Hom.: 0

Bravo AF: 0.00250

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00140 AC: 170

EpiCase AF: 0.00185

EpiControl AF: 0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELENBP1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 02, 2023

This variant is classified as likely 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	Benign	0.052
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.3
DANN	Benign	0.72
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0061	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.70	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.59	N;N;.
REVEL	Benign	0.045
Sift	Benign	0.13	T;T;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.19
MVP		0.030
MPC		0.084
ClinPred		0.0035	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.35

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: rs146726959; hg19: chr1-151337690;