rs1110144

Variant names:

• chr7-148304199-G-A
• rs1110144
• NM_014141.6:c.3475+37073G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-148304199-G-A
• chr7-148304199-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.3475+37073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,076 control chromosomes in the GnomAD database, including 11,245 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 0.37 (11245 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 11 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: G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014141.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.3475+37073G>A		intron	N/A	NP_054860.1	A0A090N7T7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.3475+37073G>A		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000628930.2	TSL:2	c.652+37073G>A		intron	N/A	ENSP00000487516.1	B7Z1Y6
	CNTNAP2	ENST00000627772.2	TSL:2	n.1648+37073G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55837 AN: 151958 Hom.: 11221 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.368 AC: 55910 AN: 152076 Hom.: 11245 Cov.: 33 AF XY: 0.366 AC XY: 27206 AN XY: 74348

African (AFR) AF: 0.541 AC: 22449 AN: 41458

American (AMR) AF: 0.273 AC: 4176 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1227 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1266 AN: 5182

South Asian (SAS) AF: 0.402 AC: 1941 AN: 4824

European-Finnish (FIN) AF: 0.308 AC: 3255 AN: 10556

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20501 AN: 67974

Other (OTH) AF: 0.349 AC: 736 AN: 2110

Alfa AF: 0.310 Hom.: 10133

Bravo AF: 0.367

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.73
PhyloP100		-0.42
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: rs1110144; hg19: chr7-148001291; COSMIC: COSV107474651;