11-119677988-T-G

Variant names:

• chr11-119677988-T-G
• rs2292293
• NM_002855.5:c.431-131A>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.431-131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 884,476 control chromosomes in the GnomAD database, including 74,934 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 0.43 (14287 hom., cov: 33)
  • Exomes 𝑓: 0.40 (60647 hom.)
• Consequence: NECTIN1 NM_002855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.431-131A>C		intron_variant	Intron 2 of 5	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.431-131A>C		intron_variant	Intron 2 of 7		NP_976030.1
NECTIN1	NM_203286.2	c.431-131A>C		intron_variant	Intron 2 of 5		NP_976031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.431-131A>C		intron_variant	Intron 2 of 5	1	NM_002855.5	ENSP00000264025.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65033 AN: 151944 Hom.: 14239 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.399 AC: 292462 AN: 732414 Hom.: 60647 AF XY: 0.393 AC XY: 151604 AN XY: 385442

African (AFR) AF: 0.460 AC: 8782 AN: 19106

American (AMR) AF: 0.556 AC: 19612 AN: 35252

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 7522 AN: 20954

East Asian (EAS) AF: 0.524 AC: 17277 AN: 32982

South Asian (SAS) AF: 0.324 AC: 21391 AN: 65962

European-Finnish (FIN) AF: 0.449 AC: 15979 AN: 35618

Middle Eastern (MID) AF: 0.443 AC: 1826 AN: 4124

European-Non Finnish (NFE) AF: 0.384 AC: 185008 AN: 481872

Other (OTH) AF: 0.412 AC: 15065 AN: 36544

GnomAD4 genome AF: 0.428 AC: 65153 AN: 152062 Hom.: 14287 Cov.: 33 AF XY: 0.434 AC XY: 32248 AN XY: 74338

African (AFR) AF: 0.461 AC: 19130 AN: 41466

American (AMR) AF: 0.495 AC: 7575 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1219 AN: 3462

East Asian (EAS) AF: 0.535 AC: 2767 AN: 5168

South Asian (SAS) AF: 0.346 AC: 1663 AN: 4812

European-Finnish (FIN) AF: 0.470 AC: 4975 AN: 10592

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26569 AN: 67952

Other (OTH) AF: 0.423 AC: 892 AN: 2110

Alfa AF: 0.298 Hom.: 952

Bravo AF: 0.438

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.87
DANN	Benign	0.63
PhyloP100		-0.70
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: rs2292293; hg19: chr11-119548698; COSMIC: COSV50602982; COSMIC: COSV50602982;