NM_003944.4:c.1099G>A

Variant names:

• chr1-151365227-C-T
• rs72710112
• NM_003944.4:c.1099G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/20 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25
• Publications: 14 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: MODERATE, LIMITED Submitted by: ClinGen, 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 -20 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 VariationId is 775140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 8146 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 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.1099G>A	p.Glu367Lys	missense	Exon 10 of 12	NP_003935.2
	SELENBP1	NM_001258289.2		c.1225G>A	p.Glu409Lys	missense	Exon 10 of 12	NP_001245218.1	Q13228-4
	SELENBP1	NM_001258288.2		c.913G>A	p.Glu305Lys	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.1099G>A	p.Glu367Lys	missense	Exon 10 of 12	ENSP00000357861.5	Q13228-1
	SELENBP1	ENST00000426705.6	TSL:2	c.1225G>A	p.Glu409Lys	missense	Exon 10 of 12	ENSP00000397261.2	Q13228-4
	SELENBP1	ENST00000896531.1		c.1189G>A	p.Glu397Lys	missense	Exon 11 of 13	ENSP00000566590.1

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

GnomAD2 exomes AF: 0.00930 AC: 2323 AN: 249836 AF XY: 0.00890

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 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

African (AFR) AF: 0.0157 AC: 526 AN: 33464

American (AMR) AF: 0.00893 AC: 399 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 347 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00639 AC: 550 AN: 86138

European-Finnish (FIN) AF: 0.00116 AC: 62 AN: 53392

Middle Eastern (MID) AF: 0.0193 AC: 111 AN: 5764

European-Non Finnish (NFE) AF: 0.0126 AC: 13976 AN: 1111742

Other (OTH) AF: 0.0122 AC: 738 AN: 60374

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

African (AFR) AF: 0.0156 AC: 650 AN: 41540

American (AMR) AF: 0.0110 AC: 168 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4826

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 818 AN: 68002

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0116 Hom.: 37

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.035	N
PhyloP100		1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.046
Sift	Benign	0.67	T
Sift4G	Benign	0.73	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
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: rs72710112; hg19: chr1-151337703; COSMIC: COSV64374302; COSMIC: COSV64374302;