Genetic Variant NECTIN1:c.431-131A>C (chr11-119677988-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.705

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5 link	c.431-131A>C	intron_variant	Intron 2 of 5	ENST00000264025.8	NP_002846.3	Q15223-1
NECTIN1	NM_203285.2 link	c.431-131A>C	intron_variant	Intron 2 of 7		NP_976030.1	Q15223-2
NECTIN1	NM_203286.2 link	c.431-131A>C	intron_variant	Intron 2 of 5		NP_976031.1	Q15223-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8 link	c.431-131A>C		intron_variant	Intron 2 of 5	1	NM_002855.5	ENSP00000264025.3		Q15223-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65033

AN:

151944

Hom.:

14239

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.556

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.428

AC:

65153

AN:

152062

Hom.:

14287

Cov.:

AF XY:

0.434

AC XY:

32248

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.352

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.423

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over