rs7940667

Positions:

• chr11-119639934-A-C
• chr11-119639934-A-G
• chr11-119639934-A-T

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.354

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

Verdict is Benign. Variant got -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 id is 802808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119639934-A-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
NECTIN1	NM_203285.2	c.1082T>G	p.Val361Gly	missense_variant	6/8

Ensembl

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

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

GnomAD3 exomes AF: 0.922 AC: 231548 AN: 251242 Hom.: 107185 AF XY: 0.927 AC XY: 125886 AN XY: 135840

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 SAS exome AF: 0.979

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

Gnomad4 AFR exome AF: 0.704

Gnomad4 AMR exome AF: 0.955

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.979

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.923

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

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.901

Alfa AF: 0.913 Hom.: 84986

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cleft lip/palate-ectodermal dysplasia syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P
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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7940667; hg19: chr11-119510644;