rs780049

Variant names:

• chr2-124275726-A-C
• rs780049
• NM_001367498.1:c.381+33333A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-124275726-A-C
• chr2-124275726-A-G
• chr2-124275726-A-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.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
• Publications: 7 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]

CNTNAP5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367498.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	NM_001367498.1	MANE Select	c.381+33333A>C		intron	N/A	NP_001354427.1	A0A804HKY0
	CNTNAP5	NM_130773.4		c.381+33333A>C		intron	N/A	NP_570129.1	Q8WYK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	ENST00000682447.1	MANE Select	c.381+33333A>C		intron	N/A	ENSP00000508115.1	A0A804HKY0
	CNTNAP5	ENST00000431078.1	TSL:1	c.381+33333A>C		intron	N/A	ENSP00000399013.1	Q8WYK1

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

African (AFR) AF: 0.808 AC: 33502 AN: 41478

American (AMR) AF: 0.837 AC: 12770 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2646 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4106 AN: 5146

South Asian (SAS) AF: 0.896 AC: 4323 AN: 4824

European-Finnish (FIN) AF: 0.827 AC: 8739 AN: 10572

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52777 AN: 67972

Other (OTH) AF: 0.790 AC: 1669 AN: 2112

Alfa AF: 0.787 Hom.: 153000

Bravo AF: 0.798

Asia WGS AF: 0.852 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.38
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs780049;

hg19: chr2-125033303;