ENST00000341398.6:n.1082T>G

Variant names:

• chr11-119639934-A-C
• rs7940667
• ENST00000341398.6:n.1082T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000341398.6(NECTIN1):​n.1082T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 1,614,052 control chromosomes in the GnomAD database, including 685,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58463 hom., cov: 33)
  • Exomes 𝑓: 0.93 (627170 hom.)
• Consequence: NECTIN1 ENST00000341398.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.354
• Publications: 30 publications found

Genes affected

NECTIN1 (HGNC:9706): (nectin cell adhesion molecule 1) This gene encodes an adhesion protein that plays a role in the organization of adherens junctions and tight junctions in epithelial and endothelial cells. The protein is a calcium(2+)-independent cell-cell adhesion molecule that belongs to the immunoglobulin superfamily and has 3 extracellular immunoglobulin-like loops, a single transmembrane domain (in some isoforms), and a cytoplasmic region. This protein acts as a receptor for glycoprotein D (gD) of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) and mediates viral entry into epithelial and neuronal cells. Mutations in this gene cause cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1) as well as non-syndromic cleft lip with or without cleft palate (CL/P). Alternative splicing results in multiple transcript variants encoding proteins with distinct C-termini. [provided by RefSeq, Oct 2009]

USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3091562E-6).
• BP6: Variant 11-119639934-A-C is Benign according to our data. Variant chr11-119639934-A-C is described in ClinVar as Benign. ClinVar VariationId is 802808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_203285.2	c.1082T>G	p.Val361Gly	missense_variant	Exon 6 of 8		NP_976030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000341398.6	n.1082T>G		non_coding_transcript_exon_variant	Exon 6 of 8	1
NECTIN1	ENST00000531468.2	c.1082T>G	p.Val361Gly	missense_variant	Exon 6 of 10	3		ENSP00000513010.1
USP2-AS1	ENST00000706364.1	n.953A>C		non_coding_transcript_exon_variant	Exon 5 of 7

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132526 AN: 152106 Hom.: 58431 Cov.: 33

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.922 AC: 231548 AN: 251242 AF XY: 0.927

Gnomad AFR exome AF: 0.711

Gnomad AMR exome AF: 0.958

Gnomad ASJ exome AF: 0.933

Gnomad EAS exome AF: 0.950

Gnomad FIN exome AF: 0.908

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.933

GnomAD4 exome AF: 0.926 AC: 1352931 AN: 1461828 Hom.: 627170 Cov.: 64 AF XY: 0.928 AC XY: 674746 AN XY: 727206

African (AFR) AF: 0.704 AC: 23578 AN: 33476

American (AMR) AF: 0.955 AC: 42718 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 24383 AN: 26136

East Asian (EAS) AF: 0.943 AC: 37453 AN: 39700

South Asian (SAS) AF: 0.979 AC: 84415 AN: 86258

European-Finnish (FIN) AF: 0.906 AC: 48347 AN: 53390

Middle Eastern (MID) AF: 0.918 AC: 5297 AN: 5768

European-Non Finnish (NFE) AF: 0.927 AC: 1031023 AN: 1111980

Other (OTH) AF: 0.923 AC: 55717 AN: 60396

GnomAD4 genome AF: 0.871 AC: 132612 AN: 152224 Hom.: 58463 Cov.: 33 AF XY: 0.874 AC XY: 65049 AN XY: 74432

African (AFR) AF: 0.718 AC: 29799 AN: 41524

American (AMR) AF: 0.930 AC: 14240 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3240 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4876 AN: 5170

South Asian (SAS) AF: 0.982 AC: 4740 AN: 4826

European-Finnish (FIN) AF: 0.905 AC: 9617 AN: 10626

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63036 AN: 67982

Other (OTH) AF: 0.901 AC: 1905 AN: 2114

Alfa AF: 0.907 Hom.: 186175

Bravo AF: 0.867

TwinsUK AF: 0.931 AC: 3453

ALSPAC AF: 0.920 AC: 3544

ESP6500AA AF: 0.733 AC: 3225

ESP6500EA AF: 0.931 AC: 7995

ExAC AF: 0.916 AC: 111232

Asia WGS AF: 0.946 AC: 3289 AN: 3478

EpiCase AF: 0.929

EpiControl AF: 0.929

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cleft lip/palate-ectodermal dysplasia syndrome Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.1
DANN	Benign	0.64
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.065	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.35
PROVEAN	Benign	0.090	N
REVEL	Benign	0.088
Sift	Benign	0.055	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.049
ClinPred		0.0038	T
GERP RS		1.7
Mutation Taster		=80/20	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7940667; hg19: chr11-119510644; COSMIC: COSV108174534; COSMIC: COSV108174534;