Genetic Variant NECTIN1:p.Glu444del (chr11-119664967-CCCT-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_002855.5(NECTIN1):c.1331_1333delAGG(p.Glu444del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,595,172 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

NECTIN1
NM_002855.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

Publications

4 publications found

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 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

NECTIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002855.5

BP6

Variant 11-119664967-CCCT-C is Benign according to our data. Variant chr11-119664967-CCCT-C is described in ClinVar as Benign. ClinVar VariationId is 770407.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 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.1331_1333delAGG	p.Glu444del	disruptive_inframe_deletion	Exon 6 of 6	NP_002846.3
	NECTIN1	NM_203285.2		c.1003+10189_1003+10191delAGG		intron	N/A	NP_976030.1	Q15223-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NECTIN1	ENST00000264025.8	TSL:1 MANE Select	c.1331_1333delAGG	p.Glu444del	disruptive_inframe_deletion	Exon 6 of 6	ENSP00000264025.3	Q15223-1
NECTIN1	ENST00000341398.6	TSL:1	n.1003+10189_1003+10191delAGG		intron	N/A
NECTIN1	ENST00000531468.2	TSL:3	c.1003+10189_1003+10191delAGG		intron	N/A	ENSP00000513010.1	A0A8V8TKI1

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

151534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000280

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000750

AC:

173

AN:

230564

AF XY:

0.000705

show subpopulations

Gnomad AFR exome

AF:

0.000736

Gnomad AMR exome

AF:

0.000371

Gnomad ASJ exome

AF:

0.000219

Gnomad EAS exome

AF:

0.000803

Gnomad FIN exome

AF:

0.000563

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000326

AC:

470

AN:

1443524

Hom.:

AF XY:

0.000333

AC XY:

239

AN XY:

717922

show subpopulations

African (AFR)

AF:

0.000304

AC:

AN:

32854

American (AMR)

AF:

0.000204

AC:

AN:

44102

Ashkenazi Jewish (ASJ)

AF:

0.000117

AC:

AN:

25726

East Asian (EAS)

AF:

0.000229

AC:

AN:

39332

South Asian (SAS)

AF:

0.000447

AC:

AN:

85026

European-Finnish (FIN)

AF:

0.000343

AC:

AN:

52476

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000323

AC:

355

AN:

1098688

Other (OTH)

AF:

0.000436

AC:

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000211

AC:

AN:

151648

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41394

American (AMR)

AF:

0.0000656

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000388

AC:

AN:

5150

South Asian (SAS)

AF:

0.000209

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000280

AC:

AN:

67802

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00380

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-119664967-CCCTCCTCCTCCT-CCCTCCTCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over