rs2726363

chr11-99476993-T-Achr11-99476993-T-Cchr11-99476993-T-G

Variant summary

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

The NM_014361.4(CNTN5):c.-70-79152T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 151,614 control chromosomes in the GnomAD database, including 42,888 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 0.75 (42888 hom., cov: 30)
• Consequence: CNTN5 NM_014361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4	c.-70-79152T>A		intron_variant		ENST00000524871.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6	c.-70-79152T>A		intron_variant		1	NM_014361.4	P1
CNTN5	ENST00000527185.5	c.-70-79152T>A		intron_variant		1
CNTN5	ENST00000528727.5	n.435-79152T>A		intron_variant, non_coding_transcript_variant		1
CNTN5	ENST00000528682.5	c.-70-79152T>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113340 AN: 151496 Hom.: 42862 Cov.: 30

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.748 AC: 113411 AN: 151614 Hom.: 42888 Cov.: 30 AF XY: 0.742 AC XY: 54936 AN XY: 74040

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.788

Alfa AF: 0.770 Hom.: 5315

Bravo AF: 0.757

Asia WGS AF: 0.553 AC: 1923 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.63
Dann	Benign	0.38

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: rs2726363; hg19: chr11-99347724; COSMIC: COSV73150390;