11-119664967-C-CCCTCCT

Variant names:

• chr11-119664967-C-CCCTCCT
• rs137909701
• NM_002855.5:c.1328_1333dupAGGAGG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_002855.5(NECTIN1):​c.1328_1333dupAGGAGG​(p.Glu443_Glu444dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,610,616 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (11 hom.)
• Consequence: NECTIN1 NM_002855.5 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.00
• 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002855.5
• BP6: Variant 11-119664967-C-CCCTCCT is Benign according to our data. Variant chr11-119664967-C-CCCTCCT is described in ClinVar as Benign. ClinVar VariationId is 779437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00298 (452/151674) while in subpopulation NFE AF = 0.00413 (280/67808). AF 95% confidence interval is 0.00373. There are 0 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

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.1328_1333dupAGGAGG	p.Glu443_Glu444dup	conservative_inframe_insertion	Exon 6 of 6	NP_002846.3
	NECTIN1	NM_203285.2		c.1003+10186_1003+10191dupAGGAGG		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.1328_1333dupAGGAGG	p.Glu443_Glu444dup	conservative_inframe_insertion	Exon 6 of 6	ENSP00000264025.3	Q15223-1
	NECTIN1	ENST00000341398.6	TSL:1	n.1003+10186_1003+10191dupAGGAGG		intron	N/A
	NECTIN1	ENST00000531468.2	TSL:3	c.1003+10186_1003+10191dupAGGAGG		intron	N/A	ENSP00000513010.1	A0A8V8TKI1

Frequencies

GnomAD3 genomes AF: 0.00300 AC: 454 AN: 151558 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00193

GnomAD2 exomes AF: 0.00299 AC: 689 AN: 230564 AF XY: 0.00278

Gnomad AFR exome AF: 0.000669

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000402

Gnomad FIN exome AF: 0.00942

Gnomad NFE exome AF: 0.00434

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00414 AC: 6047 AN: 1458942 Hom.: 11 Cov.: 39 AF XY: 0.00402 AC XY: 2919 AN XY: 725782

African (AFR) AF: 0.000599 AC: 20 AN: 33368

American (AMR) AF: 0.000806 AC: 36 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.000307 AC: 8 AN: 26098

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39672

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86186

European-Finnish (FIN) AF: 0.00883 AC: 469 AN: 53094

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00482 AC: 5344 AN: 1109850

Other (OTH) AF: 0.00249 AC: 150 AN: 60268

GnomAD4 genome AF: 0.00298 AC: 452 AN: 151674 Hom.: 0 Cov.: 31 AF XY: 0.00305 AC XY: 226 AN XY: 74102

African (AFR) AF: 0.000894 AC: 37 AN: 41404

American (AMR) AF: 0.00131 AC: 20 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.0105 AC: 110 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00413 AC: 280 AN: 67808

Other (OTH) AF: 0.00191 AC: 4 AN: 2098

Alfa AF: 0.00119 Hom.: 43

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	NECTIN1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=76/24	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs137909701; hg19: chr11-119535677;