rs11899928

Variant names:

• chr2-124499159-T-C
• rs11899928
• NM_001367498.1:c.1063-5133T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1063-5133T>C		intron_variant	Intron 7 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1060-5133T>C		intron_variant	Intron 7 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.1063-5133T>C		intron_variant	Intron 7 of 22		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.1063-5133T>C		intron_variant	Intron 7 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.1060-5133T>C		intron_variant	Intron 7 of 23	1		ENSP00000399013.1

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

African (AFR) AF: 0.0483 AC: 2004 AN: 41530

American (AMR) AF: 0.00681 AC: 104 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4818

European-Finnish (FIN) AF: 0.00585 AC: 62 AN: 10604

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0109 AC: 741 AN: 68030

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0285 Hom.: 54

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
PhyloP100		-3.1
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: rs11899928; hg19: chr2-125256736;