rs780049

Positions:

• chr2-124275726-A-C
• chr2-124275726-A-G
• chr2-124275726-A-T

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.381+33333A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,040 control chromosomes in the GnomAD database, including 48,677 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 0.80 (48677 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP5	NM_001367498.1	c.381+33333A>C		intron_variant		ENST00000682447.1
CNTNAP5	NM_130773.4	c.381+33333A>C		intron_variant
CNTNAP5	XM_017003316.2	c.381+33333A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.381+33333A>C		intron_variant			NM_001367498.1	A1
CNTNAP5	ENST00000431078.1	c.381+33333A>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121423 AN: 151922 Hom.: 48629 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.799 AC: 121523 AN: 152040 Hom.: 48677 Cov.: 32 AF XY: 0.803 AC XY: 59665 AN XY: 74270

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.790

Alfa AF: 0.784 Hom.: 97098

Bravo AF: 0.798

Asia WGS AF: 0.852 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
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: rs780049; hg19: chr2-125033303;