rs6970064

Variant names:

• chr7-147505273-G-A
• rs6970064
• NM_014141.6:c.1777+19232G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147505273-G-A
• chr7-147505273-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014141.6(CNTNAP2):​c.1777+19232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 150,666 control chromosomes in the GnomAD database, including 12,583 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 0.40 (12583 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1777+19232G>A		intron_variant	Intron 11 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1777+19232G>A		intron_variant	Intron 11 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1777+19232G>A		intron_variant	Intron 11 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000636870.1	n.1639+19232G>A		intron_variant	Intron 9 of 21	5
CNTNAP2	ENST00000637825.1	n.1260+19232G>A		intron_variant	Intron 8 of 13	5
CNTNAP2	ENST00000638117.1	n.1680+19232G>A		intron_variant	Intron 10 of 12	5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60010 AN: 150552 Hom.: 12581 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.398 AC: 60030 AN: 150666 Hom.: 12583 Cov.: 32 AF XY: 0.389 AC XY: 28684 AN XY: 73654

African (AFR) AF: 0.442 AC: 17745 AN: 40182

American (AMR) AF: 0.292 AC: 4442 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3470

East Asian (EAS) AF: 0.144 AC: 748 AN: 5180

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4828

European-Finnish (FIN) AF: 0.375 AC: 3951 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 95 AN: 288

European-Non Finnish (NFE) AF: 0.433 AC: 29423 AN: 67956

Other (OTH) AF: 0.369 AC: 771 AN: 2092

Alfa AF: 0.365 Hom.: 2692

Bravo AF: 0.400

Asia WGS AF: 0.216 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.59
PhyloP100		1.1
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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs6970064; hg19: chr7-147202365;