rs1835353

Positions:

• chr2-124406250-G-T

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.382-11193G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,170 control chromosomes in the GnomAD database, including 1,942 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 0.15 (1942 hom., cov: 33)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.382-11193G>T		intron_variant		ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.382-11193G>T		intron_variant			NP_570129.1
CNTNAP5	XM_017003316.2	c.382-11193G>T		intron_variant			XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.382-11193G>T		intron_variant			NM_001367498.1	ENSP00000508115	A1
CNTNAP5	ENST00000431078.1	c.382-11193G>T		intron_variant		1		ENSP00000399013	P4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23514 AN: 152052 Hom.: 1939 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.155 AC: 23537 AN: 152170 Hom.: 1942 Cov.: 33 AF XY: 0.153 AC XY: 11400 AN XY: 74402

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0278

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.144

Alfa AF: 0.174 Hom.: 3260

Bravo AF: 0.143

Asia WGS AF: 0.0780 AC: 272 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.50
DANN	Benign	0.29

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: rs1835353; hg19: chr2-125163827;