rs11899928

Positions:

• chr2-124499159-T-C

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.1063-5133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,228 control chromosomes in the GnomAD database, including 52 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 0.020 (52 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

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 afr. gnomad4 allele frequency = 0.0196 (2979/152228) while in subpopulation AFR AF= 0.0483 (2004/41530). AF 95% confidence interval is 0.0465. There are 52 homozygotes in gnomad4. There are 1406 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1063-5133T>C		intron_variant		ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1060-5133T>C		intron_variant			NP_570129.1
CNTNAP5	XM_017003316.2	c.1063-5133T>C		intron_variant			XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.1063-5133T>C		intron_variant			NM_001367498.1	ENSP00000508115	A1
CNTNAP5	ENST00000431078.1	c.1060-5133T>C		intron_variant		1		ENSP00000399013	P4

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2972 AN: 152112 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0196 AC: 2979 AN: 152228 Hom.: 52 Cov.: 32 AF XY: 0.0189 AC XY: 1406 AN XY: 74422

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.00681

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00585

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0144 Hom.: 7

Bravo AF: 0.0202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.059
DANN	Benign	0.51

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: rs11899928; hg19: chr2-125256736;