11-119716385-C-T

Variant names:

• chr11-119716385-C-T
• rs12416901
• NM_002855.5:c.79+12090G>A

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+12090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,190 control chromosomes in the GnomAD database, including 69,685 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 0.96 (69685 hom., cov: 31)
• Consequence: NECTIN1 NM_002855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.79+12090G>A		intron_variant	Intron 1 of 5	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.79+12090G>A		intron_variant	Intron 1 of 7		NP_976030.1
NECTIN1	NM_203286.2	c.79+12090G>A		intron_variant	Intron 1 of 5		NP_976031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.79+12090G>A		intron_variant	Intron 1 of 5	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000340882.2	c.79+12090G>A		intron_variant	Intron 1 of 5	1		ENSP00000345289.2
NECTIN1	ENST00000341398.6	n.79+12090G>A		intron_variant	Intron 1 of 7	1
NECTIN1	ENST00000531468.2	c.79+12090G>A		intron_variant	Intron 1 of 9	3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145479 AN: 152072 Hom.: 69640 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.957 AC: 145580 AN: 152190 Hom.: 69685 Cov.: 31 AF XY: 0.956 AC XY: 71145 AN XY: 74404

African (AFR) AF: 0.930 AC: 38612 AN: 41510

American (AMR) AF: 0.962 AC: 14723 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3302 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4559 AN: 5138

South Asian (SAS) AF: 0.979 AC: 4719 AN: 4822

European-Finnish (FIN) AF: 0.974 AC: 10333 AN: 10610

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66160 AN: 68016

Other (OTH) AF: 0.953 AC: 2014 AN: 2114

Alfa AF: 0.966 Hom.: 27857

Bravo AF: 0.955

Asia WGS AF: 0.953 AC: 3314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		0.30
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: rs12416901; hg19: chr11-119587095;