rs4726793

Variant names:

• chr7-146579798-G-A
• rs4726793
• NM_014141.6:c.98-194473G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-146579798-G-A
• chr7-146579798-G-T

Variant summary

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

The NM_014141.6(CNTNAP2):​c.98-194473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,098 control chromosomes in the GnomAD database, including 49,760 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 0.80 (49760 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 3 publications found

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

CNTNAP2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, NO_KNOWN Submitted by: ClinGen
• cortical dysplasia-focal epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.98-194473G>A		intron_variant	Intron 1 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.98-194473G>A		intron_variant	Intron 1 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.98-194473G>A		intron_variant	Intron 1 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000625365.2	c.98-194473G>A		intron_variant	Intron 2 of 3	5		ENSP00000485955.1
CNTNAP2	ENST00000637150.1	n.27-194473G>A		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122263 AN: 151980 Hom.: 49718 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.804 AC: 122357 AN: 152098 Hom.: 49760 Cov.: 32 AF XY: 0.804 AC XY: 59755 AN XY: 74334

African (AFR) AF: 0.871 AC: 36167 AN: 41512

American (AMR) AF: 0.624 AC: 9506 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2759 AN: 3472

East Asian (EAS) AF: 0.675 AC: 3480 AN: 5158

South Asian (SAS) AF: 0.881 AC: 4245 AN: 4818

European-Finnish (FIN) AF: 0.850 AC: 8995 AN: 10588

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54601 AN: 67998

Other (OTH) AF: 0.769 AC: 1621 AN: 2108

Alfa AF: 0.781 Hom.: 7309

Bravo AF: 0.787

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.49
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4726793; hg19: chr7-146276890;