rs7104562

Variant names:

• chr11-119706614-G-A
• rs7104562
• NM_002855.5:c.79+21861C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119706614-G-A
• chr11-119706614-G-C

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+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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.79+21861C>T		intron_variant	Intron 1 of 5	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.79+21861C>T		intron_variant	Intron 1 of 7		NP_976030.1
NECTIN1	NM_203286.2	c.79+21861C>T		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+21861C>T		intron_variant	Intron 1 of 5	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000340882.2	c.79+21861C>T		intron_variant	Intron 1 of 5	1		ENSP00000345289.2
NECTIN1	ENST00000341398.6	n.79+21861C>T		intron_variant	Intron 1 of 7	1
NECTIN1	ENST00000531468.2	c.79+21861C>T		intron_variant	Intron 1 of 9	3		ENSP00000513010.1

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

African (AFR) AF: 0.767 AC: 31834 AN: 41518

American (AMR) AF: 0.939 AC: 14375 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3265 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4639 AN: 5178

South Asian (SAS) AF: 0.978 AC: 4715 AN: 4822

European-Finnish (FIN) AF: 0.982 AC: 10430 AN: 10618

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66186 AN: 68040

Other (OTH) AF: 0.919 AC: 1944 AN: 2116

Alfa AF: 0.947 Hom.: 23268

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
PhyloP100		0.11
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: rs7104562; hg19: chr11-119577324;