11-119638779-C-T

Variant names:

• chr11-119638779-C-T
• rs144913704
• ENST00000341398.6:n.1179G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_203285.2(NECTIN1):​c.1179G>A​(p.Pro393Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,613,966 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: NECTIN1 NM_203285.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

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]

USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

LOC105369520 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-119638779-C-T is Benign according to our data. Variant chr11-119638779-C-T is described in ClinVar as [Benign]. Clinvar id is 2696692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.023 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00182 (277/152258) while in subpopulation NFE AF= 0.00194 (132/68012). AF 95% confidence interval is 0.00167. There are 0 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_203285.2	c.1179G>A	p.Pro393Pro	synonymous_variant	Exon 7 of 8		NP_976030.1
LOC105369520	XR_001748413.1	n.269-717C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000341398.6	n.1179G>A		non_coding_transcript_exon_variant	Exon 7 of 8	1
NECTIN1	ENST00000531468.2	c.1179G>A	p.Pro393Pro	synonymous_variant	Exon 7 of 10	3		ENSP00000513010.1
USP2-AS1	ENST00000706364.1	n.515-717C>T		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.00913

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00187 AC: 469 AN: 250350 Hom.: 1 AF XY: 0.00184 AC XY: 249 AN XY: 135412

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000785

Gnomad FIN exome AF: 0.00993

Gnomad NFE exome AF: 0.00185

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00151 AC: 2212 AN: 1461708 Hom.: 3 Cov.: 32 AF XY: 0.00151 AC XY: 1096 AN XY: 727138

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000719

Gnomad4 FIN exome AF: 0.00847

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74432

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.00913

Gnomad4 NFE AF: 0.00194

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00146

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 04, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144913704; hg19: chr11-119509489;