rs1477841

Variant names:

• chr3-111174420-C-T
• rs1477841
• NM_001243288.2:c.1222-17931C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243288.2(NECTIN3):​c.1222-17931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,912 control chromosomes in the GnomAD database, including 12,323 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 0.29 (12323 hom., cov: 31)
• Consequence: NECTIN3 NM_001243288.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 3 publications found

Genes affected

NECTIN3 (HGNC:17664): (nectin cell adhesion molecule 3) This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243288.2. 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
	NECTIN3	NM_001243288.2		c.1222-17931C>T		intron	N/A	NP_001230217.1	Q9NQS3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN3	ENST00000493615.5	TSL:2	c.1222-17931C>T		intron	N/A	ENSP00000420579.1	Q9NQS3-3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44613 AN: 151794 Hom.: 12283 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.294 AC: 44712 AN: 151912 Hom.: 12323 Cov.: 31 AF XY: 0.297 AC XY: 22070 AN XY: 74232

African (AFR) AF: 0.708 AC: 29338 AN: 41410

American (AMR) AF: 0.252 AC: 3845 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2695 AN: 5126

South Asian (SAS) AF: 0.123 AC: 594 AN: 4818

European-Finnish (FIN) AF: 0.200 AC: 2115 AN: 10556

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.0731 AC: 4965 AN: 67950

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.155 Hom.: 11880

Bravo AF: 0.320

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.78
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1477841; hg19: chr3-110893267;