rs1547597

Positions:

• chr7-148269658-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014141.6(CNTNAP2):​c.3475+2532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,188 control chromosomes in the GnomAD database, including 43,979 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 0.76 (43979 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.3475+2532G>A		intron_variant		ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.3475+2532G>A		intron_variant		1	NM_014141.6	ENSP00000354778	P1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115434 AN: 152070 Hom.: 43956 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.759 AC: 115502 AN: 152188 Hom.: 43979 Cov.: 32 AF XY: 0.767 AC XY: 57035 AN XY: 74394

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.773

Alfa AF: 0.760 Hom.: 7428

Bravo AF: 0.752

Asia WGS AF: 0.830 AC: 2884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	15
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1547597; hg19: chr7-147966750;