2-124370219-C-T

Variant names:

• chr2-124370219-C-T
• rs779984
• NM_001367498.1:c.382-47224C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367498.1(CNTNAP5):​c.382-47224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,164 control chromosomes in the GnomAD database, including 1,594 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 0.14 (1594 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.382-47224C>T		intron_variant	Intron 3 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.382-47224C>T		intron_variant	Intron 3 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.382-47224C>T		intron_variant	Intron 3 of 22		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.382-47224C>T		intron_variant	Intron 3 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.382-47224C>T		intron_variant	Intron 3 of 23	1		ENSP00000399013.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21011 AN: 152046 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.138 AC: 21028 AN: 152164 Hom.: 1594 Cov.: 32 AF XY: 0.138 AC XY: 10234 AN XY: 74396

African (AFR) AF: 0.156 AC: 6459 AN: 41530

American (AMR) AF: 0.103 AC: 1574 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.108 AC: 556 AN: 5168

South Asian (SAS) AF: 0.0822 AC: 397 AN: 4830

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9466 AN: 67994

Other (OTH) AF: 0.145 AC: 305 AN: 2110

Alfa AF: 0.135 Hom.: 823

Bravo AF: 0.136

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.51
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs779984; hg19: chr2-125127796;