rs6973370

Variant names:

• chr7-147331835-A-G
• rs6973370
• NM_014141.6:c.1498+31545A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-147331835-A-G
• chr7-147331835-A-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.1498+31545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,926 control chromosomes in the GnomAD database, including 11,811 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 0.39 (11811 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1498+31545A>G		intron_variant	Intron 9 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1498+31545A>G		intron_variant	Intron 9 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1498+31545A>G		intron_variant	Intron 9 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59002 AN: 151808 Hom.: 11791 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.389 AC: 59066 AN: 151926 Hom.: 11811 Cov.: 32 AF XY: 0.393 AC XY: 29153 AN XY: 74250

African (AFR) AF: 0.324 AC: 13436 AN: 41422

American (AMR) AF: 0.409 AC: 6236 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1880 AN: 5148

South Asian (SAS) AF: 0.490 AC: 2353 AN: 4804

European-Finnish (FIN) AF: 0.457 AC: 4831 AN: 10564

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.413 AC: 28085 AN: 67938

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.379 Hom.: 1411

Bravo AF: 0.377

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.79
DANN	Benign	0.42
PhyloP100		-1.6
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: rs6973370; hg19: chr7-147028927;