rs3833765

chr11-119664967-CCCT-Cchr11-119664967-CCCTCCT-Cchr11-119664967-CCCTCCTCCTCCT-Cchr11-119664967-CCCTCCTCCT-Cchr11-119664967-C-CCCTchr11-119664967-C-CCCTCCTchr11-119664967-C-CCCTCCTCCTCCTchr11-119664967-C-CCCTCCTCCT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002855.5(NECTIN1):c.1331_1333del(p.Glu444del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,595,172 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: NECTIN1 NM_002855.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 11-119664967-CCCT-C is Benign according to our data. Variant chr11-119664967-CCCT-C is described in ClinVar as [Benign]. Clinvar id is 770407.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-119664967-CCCT-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECTIN1	NM_002855.5	c.1331_1333del	p.Glu444del	inframe_deletion	6/6	ENST00000264025.8
NECTIN1	NM_203285.2	c.1003+10189_1003+10191del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN1	ENST00000264025.8	c.1331_1333del	p.Glu444del	inframe_deletion	6/6	1	NM_002855.5	P1
NECTIN1	ENST00000341398.6	n.1003+10189_1003+10191del		intron_variant, non_coding_transcript_variant		1
NECTIN1	ENST00000531468.2	c.1003+10189_1003+10191del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 31 AN: 151534 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000750 AC: 173 AN: 230564 Hom.: 1 AF XY: 0.000705 AC XY: 88 AN XY: 124844

Gnomad AFR exome AF: 0.000736

Gnomad AMR exome AF: 0.000371

Gnomad ASJ exome AF: 0.000219

Gnomad EAS exome AF: 0.000803

Gnomad SAS exome AF: 0.000642

Gnomad FIN exome AF: 0.000563

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.000326 AC: 470 AN: 1443524 Hom.: 2 AF XY: 0.000333 AC XY: 239 AN XY: 717922

Gnomad4 AFR exome AF: 0.000304

Gnomad4 AMR exome AF: 0.000204

Gnomad4 ASJ exome AF: 0.000117

Gnomad4 EAS exome AF: 0.000229

Gnomad4 SAS exome AF: 0.000447

Gnomad4 FIN exome AF: 0.000343

Gnomad4 NFE exome AF: 0.000323

Gnomad4 OTH exome AF: 0.000436

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151648 Hom.: 0 Cov.: 31 AF XY: 0.000216 AC XY: 16 AN XY: 74080

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs137909701; hg19: chr11-119535677;