11-119676295-A-G

Variant names:

• chr11-119676295-A-G
• rs7122134
• NM_002855.5:c.851+807T>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.851+807T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,118 control chromosomes in the GnomAD database, including 26,368 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 0.56 (26368 hom., cov: 33)
• Consequence: NECTIN1 NM_002855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.851+807T>C		intron_variant	Intron 4 of 5	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.851+807T>C		intron_variant	Intron 4 of 7		NP_976030.1
NECTIN1	NM_203286.2	c.851+807T>C		intron_variant	Intron 4 of 5		NP_976031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.851+807T>C		intron_variant	Intron 4 of 5	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000340882.2	c.851+807T>C		intron_variant	Intron 4 of 5	1		ENSP00000345289.2
NECTIN1	ENST00000341398.6	n.851+807T>C		intron_variant	Intron 4 of 7	1
NECTIN1	ENST00000531468.2	c.851+807T>C		intron_variant	Intron 4 of 9	3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85798 AN: 151998 Hom.: 26303 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.565 AC: 85933 AN: 152118 Hom.: 26368 Cov.: 33 AF XY: 0.567 AC XY: 42174 AN XY: 74350

African (AFR) AF: 0.810 AC: 33625 AN: 41514

American (AMR) AF: 0.571 AC: 8738 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1927 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3225 AN: 5168

South Asian (SAS) AF: 0.446 AC: 2150 AN: 4818

European-Finnish (FIN) AF: 0.490 AC: 5171 AN: 10552

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29541 AN: 67986

Other (OTH) AF: 0.543 AC: 1144 AN: 2108

Alfa AF: 0.306 Hom.: 624

Bravo AF: 0.587

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.43
PhyloP100		-0.33
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: rs7122134; hg19: chr11-119547005;