chr1-151365214-G-C

Variant names:

• chr1-151365214-G-C
• rs146726959
• NM_003944.4:c.1112C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). 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 criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.945
• Publications: 4 publications found

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]

SELENBP1 Gene-Disease associations (from GenCC):

• extraoral halitosis due to methanethiol oxidase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia, Ambry Genetics
• autosomal recessive extra-oral halitosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 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 VariationId is 3045077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003944.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	NM_003944.4	MANE Select	c.1112C>G	p.Ser371Cys	missense	Exon 10 of 12	NP_003935.2
	SELENBP1	NM_001258289.2		c.1238C>G	p.Ser413Cys	missense	Exon 10 of 12	NP_001245218.1	Q13228-4
	SELENBP1	NM_001258288.2		c.926C>G	p.Ser309Cys	missense	Exon 9 of 11	NP_001245217.1	Q13228-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENBP1	ENST00000368868.10	TSL:1 MANE Select	c.1112C>G	p.Ser371Cys	missense	Exon 10 of 12	ENSP00000357861.5	Q13228-1
	SELENBP1	ENST00000426705.6	TSL:2	c.1238C>G	p.Ser413Cys	missense	Exon 10 of 12	ENSP00000397261.2	Q13228-4
	SELENBP1	ENST00000896531.1		c.1202C>G	p.Ser401Cys	missense	Exon 11 of 13	ENSP00000566590.1

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

GnomAD2 exomes AF: 0.00140 AC: 350 AN: 250424 AF XY: 0.00135

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 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

African (AFR) AF: 0.000269 AC: 9 AN: 33468

American (AMR) AF: 0.000828 AC: 37 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86168

European-Finnish (FIN) AF: 0.00206 AC: 110 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00191 AC: 2122 AN: 1111886

Other (OTH) AF: 0.00147 AC: 89 AN: 60388

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

African (AFR) AF: 0.000505 AC: 21 AN: 41570

American (AMR) AF: 0.00517 AC: 79 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00201 AC: 137 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SELENBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.70	N
PhyloP100		-0.94
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.045
Sift	Benign	0.13	T
Sift4G	Benign	0.11	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
Mutation Taster		=100/0	polymorphism

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: rs146726959; hg19: chr1-151337690;