rs3833765

Positions:

• chr11-119664967-C-CCCTCCT
• chr11-119664967-CCCTCCT-C
• chr11-119664967-C-CCCT
• chr11-119664967-C-CCCTCCTCCT
• chr11-119664967-CCCTCCTCCT-C
• chr11-119664967-CCCT-C
• chr11-119664967-CCCTCCTCCTCCT-C
• chr11-119664967-C-CCCTCCTCCTCCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002855.5(NECTIN1):​c.1328_1333dupAGGAGG​(p.Glu443_Glu444dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,610,616 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (11 hom.)
• Consequence: NECTIN1 NM_002855.5 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-119664967-C-CCCTCCT is Benign according to our data. Variant chr11-119664967-C-CCCTCCT is described in ClinVar as [Benign]. Clinvar id is 779437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00298 (452/151674) while in subpopulation NFE AF= 0.00413 (280/67808). AF 95% confidence interval is 0.00373. There are 0 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.1328_1333dupAGGAGG	p.Glu443_Glu444dup	conservative_inframe_insertion	6/6	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.1003+10186_1003+10191dupAGGAGG		intron_variant			NP_976030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.1328_1333dupAGGAGG	p.Glu443_Glu444dup	conservative_inframe_insertion	6/6	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000341398.6	n.1003+10186_1003+10191dupAGGAGG		intron_variant		1
NECTIN1	ENST00000531468.2	c.1003+10186_1003+10191dupAGGAGG		intron_variant		3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.00300 AC: 454 AN: 151558 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.00299 AC: 689 AN: 230564 Hom.: 0 AF XY: 0.00278 AC XY: 347 AN XY: 124844

Gnomad AFR exome AF: 0.000669

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000402

Gnomad SAS exome AF: 0.000178

Gnomad FIN exome AF: 0.00942

Gnomad NFE exome AF: 0.00434

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00414 AC: 6047 AN: 1458942 Hom.: 11 Cov.: 39 AF XY: 0.00402 AC XY: 2919 AN XY: 725782

Gnomad4 AFR exome AF: 0.000599

Gnomad4 AMR exome AF: 0.000806

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00883

Gnomad4 NFE exome AF: 0.00482

Gnomad4 OTH exome AF: 0.00249

GnomAD4 genome AF: 0.00298 AC: 452 AN: 151674 Hom.: 0 Cov.: 31 AF XY: 0.00305 AC XY: 226 AN XY: 74102

Gnomad4 AFR AF: 0.000894

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.00413

Gnomad4 OTH AF: 0.00191

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

NECTIN1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs137909701; hg19: chr11-119535677;