2-124225479-T-C

Variant names:

• chr2-124225479-T-C
• rs1170612
• NM_001367498.1:c.187+3670T>C

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.187+3670T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,118 control chromosomes in the GnomAD database, including 47,039 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 0.78 (47039 hom., cov: 33)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.187+3670T>C		intron_variant	Intron 2 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.187+3670T>C		intron_variant	Intron 2 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.187+3670T>C		intron_variant	Intron 2 of 22		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.187+3670T>C		intron_variant	Intron 2 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.187+3670T>C		intron_variant	Intron 2 of 23	1		ENSP00000399013.1
CNTNAP5	ENST00000470921.1	n.105+3670T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119229 AN: 152000 Hom.: 47005 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.784 AC: 119319 AN: 152118 Hom.: 47039 Cov.: 33 AF XY: 0.790 AC XY: 58718 AN XY: 74354

African (AFR) AF: 0.738 AC: 30607 AN: 41490

American (AMR) AF: 0.818 AC: 12480 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5153 AN: 5170

South Asian (SAS) AF: 0.921 AC: 4444 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8348 AN: 10596

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53075 AN: 67992

Other (OTH) AF: 0.777 AC: 1643 AN: 2114

Alfa AF: 0.781 Hom.: 34015

Bravo AF: 0.782

Asia WGS AF: 0.954 AC: 3319 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	0.83
DANN	Benign	0.55
PhyloP100		-1.1
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: rs1170612; hg19: chr2-124983056;