chr2-124043657-G-T

Variant names:

• chr2-124043657-G-T
• rs12711664
• NM_001367498.1:c.82+17925G>T

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.82+17925G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,998 control chromosomes in the GnomAD database, including 34,281 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 0.67 (34281 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 4 publications found

Genes affected

CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function 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, and thrombospondin N-terminal-like domains. [provided by RefSeq, Jul 2008]

CNTNAP5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367498.1. 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
	CNTNAP5	NM_001367498.1	MANE Select	c.82+17925G>T		intron	N/A	NP_001354427.1	A0A804HKY0
	CNTNAP5	NM_130773.4		c.82+17925G>T		intron	N/A	NP_570129.1	Q8WYK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	ENST00000682447.1	MANE Select	c.82+17925G>T		intron	N/A	ENSP00000508115.1	A0A804HKY0
	CNTNAP5	ENST00000431078.1	TSL:1	c.82+17925G>T		intron	N/A	ENSP00000399013.1	Q8WYK1
	CNTNAP5	ENST00000423939.2	TSL:4	n.446+17925G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101909 AN: 151884 Hom.: 34251 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.671 AC: 101989 AN: 151998 Hom.: 34281 Cov.: 32 AF XY: 0.674 AC XY: 50039 AN XY: 74278

African (AFR) AF: 0.714 AC: 29599 AN: 41474

American (AMR) AF: 0.730 AC: 11142 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2148 AN: 3466

East Asian (EAS) AF: 0.679 AC: 3503 AN: 5156

South Asian (SAS) AF: 0.614 AC: 2951 AN: 4810

European-Finnish (FIN) AF: 0.686 AC: 7239 AN: 10550

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.634 AC: 43087 AN: 67954

Other (OTH) AF: 0.684 AC: 1446 AN: 2114

Alfa AF: 0.653 Hom.: 27807

Bravo AF: 0.680

Asia WGS AF: 0.637 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.55
PhyloP100		-0.31
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: rs12711664; hg19: chr2-124801234;