11-119664967-C-CCCT

Position:

• chr11-119664967-C-CCCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002855.5(NECTIN1):​c.1331_1333dupAGG​(p.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 0.0781 in 1,610,534 control chromosomes in the GnomAD database, including 4,396 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (394 hom., cov: 31)
  • Exomes 𝑓: 0.080 (4002 hom.)
• Consequence: NECTIN1 NM_002855.5 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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 -16 ACMG points.

• BP6: Variant 11-119664967-C-CCCT is Benign according to our data. Variant chr11-119664967-C-CCCT is described in ClinVar as [Benign]. Clinvar id is 218617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.1331_1333dupAGG	p.Glu444dup	conservative_inframe_insertion	6/6	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.1003+10189_1003+10191dupAGG		intron_variant			NP_976030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.1331_1333dupAGG	p.Glu444dup	conservative_inframe_insertion	6/6	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000341398.6	n.1003+10189_1003+10191dupAGG		intron_variant		1
NECTIN1	ENST00000531468.2	c.1003+10189_1003+10191dupAGG		intron_variant		3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8900 AN: 151530 Hom.: 394 Cov.: 31

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.0177

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.0448

GnomAD3 exomes AF: 0.0626 AC: 14437 AN: 230564 Hom.: 296 AF XY: 0.0632 AC XY: 7892 AN XY: 124844

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0253

Gnomad EAS exome AF: 0.0484

Gnomad SAS exome AF: 0.0204

Gnomad FIN exome AF: 0.0865

Gnomad NFE exome AF: 0.0925

Gnomad OTH exome AF: 0.0689

GnomAD4 exome AF: 0.0801 AC: 116885 AN: 1458888 Hom.: 4002 Cov.: 39 AF XY: 0.0783 AC XY: 56821 AN XY: 725744

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0277

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.0343

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.0841

Gnomad4 NFE exome AF: 0.0928

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.0587 AC: 8905 AN: 151646 Hom.: 394 Cov.: 31 AF XY: 0.0576 AC XY: 4269 AN XY: 74086

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.0924

Gnomad4 OTH AF: 0.0448

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jun 25, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2021	This variant is associated with the following publications: (PMID: 16122939, 27884173) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cleft lip/palate-ectodermal dysplasia syndrome Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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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;