11-119728019-G-C

Variant names:

• chr11-119728019-G-C
• rs3829260
• NM_002855.5:c.79+456C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002855.5(NECTIN1):​c.79+456C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,876 control chromosomes in the GnomAD database, including 16,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (16005 hom., cov: 32)
• Consequence: NECTIN1 NM_002855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 3 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]

NECTIN1 Gene-Disease associations (from GenCC):

• cleft lip/palate-ectodermal dysplasia syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN1	NM_002855.5	MANE Select	c.79+456C>G		intron	N/A	NP_002846.3
	NECTIN1	NM_203285.2		c.79+456C>G		intron	N/A	NP_976030.1
	NECTIN1	NM_203286.2		c.79+456C>G		intron	N/A	NP_976031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN1	ENST00000264025.8	TSL:1 MANE Select	c.79+456C>G		intron	N/A	ENSP00000264025.3
	NECTIN1	ENST00000340882.2	TSL:1	c.79+456C>G		intron	N/A	ENSP00000345289.2
	NECTIN1	ENST00000341398.6	TSL:1	n.79+456C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66863 AN: 151764 Hom.: 15995 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.441 AC: 66902 AN: 151876 Hom.: 16005 Cov.: 32 AF XY: 0.441 AC XY: 32703 AN XY: 74196

African (AFR) AF: 0.246 AC: 10179 AN: 41450

American (AMR) AF: 0.512 AC: 7819 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3464

East Asian (EAS) AF: 0.475 AC: 2435 AN: 5124

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4818

European-Finnish (FIN) AF: 0.529 AC: 5589 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35624 AN: 67864

Other (OTH) AF: 0.465 AC: 979 AN: 2106

Alfa AF: 0.470 Hom.: 2085

Bravo AF: 0.438

Asia WGS AF: 0.442 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.84
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3829260; hg19: chr11-119598729;