chr11-119706614-G-A

Position:

• chr11-119706614-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002855.5(NECTIN1):​c.79+21861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,274 control chromosomes in the GnomAD database, including 63,644 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 0.91 (63644 hom., cov: 32)
• Consequence: NECTIN1 NM_002855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.79+21861C>T		intron_variant		ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.79+21861C>T		intron_variant			NP_976030.1
NECTIN1	NM_203286.2	c.79+21861C>T		intron_variant			NP_976031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.79+21861C>T		intron_variant		1	NM_002855.5	ENSP00000264025	P1
NECTIN1	ENST00000340882.2	c.79+21861C>T		intron_variant		1		ENSP00000345289
NECTIN1	ENST00000341398.6	n.79+21861C>T		intron_variant, non_coding_transcript_variant		1
NECTIN1	ENST00000531468.2	c.79+21861C>T		intron_variant		3		ENSP00000513010

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138442 AN: 152156 Hom.: 63601 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.910 AC: 138545 AN: 152274 Hom.: 63644 Cov.: 32 AF XY: 0.911 AC XY: 67824 AN XY: 74462

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.919

Alfa AF: 0.947 Hom.: 13828

Bravo AF: 0.899

Asia WGS AF: 0.945 AC: 3289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.51

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: rs7104562; hg19: chr11-119577324;