rs975334

chr3-2804632-G-Achr3-2804632-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):c.359-14854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,992 control chromosomes in the GnomAD database, including 21,074 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 0.51 (21074 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.359-14854G>A		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.359-14854G>A		intron_variant		5	NM_175607.3	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76847 AN: 151872 Hom.: 21034 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.506 AC: 76951 AN: 151992 Hom.: 21074 Cov.: 32 AF XY: 0.513 AC XY: 38075 AN XY: 74280

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.504

Alfa AF: 0.408 Hom.: 28981

Bravo AF: 0.524

Asia WGS AF: 0.672 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.1
Dann	Benign	0.22

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

LitVar

Other links and lift over

dbSNP: rs975334; hg19: chr3-2846316; COSMIC: COSV68564030;