chr11-119661042-C-T

Variant names:

• chr11-119661042-C-T
• rs184430239
• NM_002855.5:c.*3705G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The NM_002855.5(NECTIN1):​c.*3705G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 980,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: NECTIN1 NM_002855.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.22
• Publications: 0 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000801 (122/152318) while in subpopulation AMR AF = 0.00242 (37/15308). AF 95% confidence interval is 0.0018. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN1	NM_002855.5	MANE Select	c.*3705G>A		3_prime_UTR	Exon 6 of 6	NP_002846.3
	NECTIN1	NM_203285.2		c.1003+14117G>A		intron	N/A	NP_976030.1	Q15223-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN1	ENST00000264025.8	TSL:1 MANE Select	c.*3705G>A		3_prime_UTR	Exon 6 of 6	ENSP00000264025.3	Q15223-1
	NECTIN1	ENST00000341398.6	TSL:1	n.1003+14117G>A		intron	N/A
	NECTIN1	ENST00000531468.2	TSL:3	c.1003+14117G>A		intron	N/A	ENSP00000513010.1	A0A8V8TKI1

Frequencies

GnomAD3 genomes AF: 0.000802 AC: 122 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000484 AC: 401 AN: 828592 Hom.: 0 Cov.: 24 AF XY: 0.000502 AC XY: 192 AN XY: 382834

African (AFR) AF: 0.000319 AC: 5 AN: 15652

American (AMR) AF: 0.00206 AC: 2 AN: 970

Ashkenazi Jewish (ASJ) AF: 0.000585 AC: 3 AN: 5128

East Asian (EAS) AF: 0.00 AC: 0 AN: 3600

South Asian (SAS) AF: 0.00 AC: 0 AN: 16366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 684

Middle Eastern (MID) AF: 0.00248 AC: 4 AN: 1612

European-Non Finnish (NFE) AF: 0.000490 AC: 371 AN: 757430

Other (OTH) AF: 0.000589 AC: 16 AN: 27150

GnomAD4 genome AF: 0.000801 AC: 122 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000792 AC XY: 59 AN XY: 74468

African (AFR) AF: 0.000722 AC: 30 AN: 41562

American (AMR) AF: 0.00242 AC: 37 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00112

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cleft lip/palate-ectodermal dysplasia syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		1.2

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: rs184430239; hg19: chr11-119531752;