rs10496639

Positions:

• chr2-124709932-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001367498.1(CNTNAP5):​c.2078-37297C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00757 in 152,092 control chromosomes in the GnomAD database, including 11 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 0.0076 (11 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.96).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00757 (1152/152092) while in subpopulation SAS AF= 0.0203 (98/4820). AF 95% confidence interval is 0.0171. There are 11 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.2078-37297C>T		intron_variant		ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.2075-37297C>T		intron_variant			NP_570129.1
CNTNAP5	XM_017003316.2	c.2078-37297C>T		intron_variant			XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.2078-37297C>T		intron_variant			NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.2075-37297C>T		intron_variant		1		ENSP00000399013.1

Frequencies

GnomAD3 genomes AF: 0.00756 AC: 1149 AN: 151974 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00466

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.00670

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

GnomAD4 genome AF: 0.00757 AC: 1152 AN: 152092 Hom.: 11 Cov.: 32 AF XY: 0.00687 AC XY: 511 AN XY: 74358

Gnomad4 AFR AF: 0.00246

Gnomad4 AMR AF: 0.00466

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.00208

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00762 Hom.: 1

Bravo AF: 0.00720

Asia WGS AF: 0.00491 AC: 17 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.063
DANN	Benign	0.17

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: rs10496639; hg19: chr2-125467509;