chr2-124487230-G-C

Position:

• chr2-124487230-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367498.1(CNTNAP5):​c.1062+12348G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,026 control chromosomes in the GnomAD database, including 2,806 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 0.17 (2806 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1062+12348G>C		intron_variant		ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1059+12351G>C		intron_variant			NP_570129.1
CNTNAP5	XM_017003316.2	c.1062+12348G>C		intron_variant			XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.1062+12348G>C		intron_variant			NM_001367498.1	ENSP00000508115	A1
CNTNAP5	ENST00000431078.1	c.1059+12351G>C		intron_variant		1		ENSP00000399013	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25299 AN: 151908 Hom.: 2799 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.167 AC: 25344 AN: 152026 Hom.: 2806 Cov.: 32 AF XY: 0.171 AC XY: 12684 AN XY: 74310

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0978

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.147

Alfa AF: 0.126 Hom.: 208

Bravo AF: 0.175

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs6706476; hg19: chr2-125244807;