rs4803766

Variant names:

• chr19-44867911-G-A
• rs4803766
• NM_001042724.2:c.478+2251G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44867911-G-A
• chr19-44867911-G-T

Variant summary

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

The NM_001042724.2(NECTIN2):​c.478+2251G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,760 control chromosomes in the GnomAD database, including 15,097 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 0.44 (15097 hom., cov: 30)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 24 publications found

Genes affected

NECTIN2 (HGNC:9707): (nectin cell adhesion molecule 2) This gene encodes a single-pass type I membrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain. This protein is one of the plasma membrane components of adherens junctions. It also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and it is involved in cell to cell spreading of these viruses. Variations in this gene have been associated with differences in the severity of multiple sclerosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042724.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.478+2251G>A		intron	N/A	NP_001036189.1
	NECTIN2	NM_002856.3		c.478+2251G>A		intron	N/A	NP_002847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.478+2251G>A		intron	N/A	ENSP00000252483.4
	NECTIN2	ENST00000252485.8	TSL:1	c.478+2251G>A		intron	N/A	ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66984 AN: 151642 Hom.: 15069 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.442 AC: 67054 AN: 151760 Hom.: 15097 Cov.: 30 AF XY: 0.436 AC XY: 32377 AN XY: 74176

African (AFR) AF: 0.456 AC: 18858 AN: 41332

American (AMR) AF: 0.548 AC: 8351 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3464

East Asian (EAS) AF: 0.390 AC: 2010 AN: 5148

South Asian (SAS) AF: 0.518 AC: 2492 AN: 4814

European-Finnish (FIN) AF: 0.285 AC: 3012 AN: 10550

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29216 AN: 67906

Other (OTH) AF: 0.458 AC: 967 AN: 2110

Alfa AF: 0.440 Hom.: 62505

Bravo AF: 0.461

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.68
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4803766; hg19: chr19-45371168;