rs10189889

Variant names:

• chr2-124687887-G-A
• rs10189889
• NM_001367498.1:c.2077+39929G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001367498.1(CNTNAP5):​c.2077+39929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 152,054 control chromosomes in the GnomAD database, including 46 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 0.023 (46 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 0 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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3505/152054) while in subpopulation NFE AF = 0.0318 (2163/67992). AF 95% confidence interval is 0.0307. There are 46 homozygotes in GnomAd4. There are 1593 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.2077+39929G>A		intron_variant	Intron 13 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.2074+39929G>A		intron_variant	Intron 13 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.2077+39929G>A		intron_variant	Intron 13 of 22		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.2077+39929G>A		intron_variant	Intron 13 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.2074+39929G>A		intron_variant	Intron 13 of 23	1		ENSP00000399013.1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3504 AN: 151940 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0231 AC: 3505 AN: 152054 Hom.: 46 Cov.: 32 AF XY: 0.0214 AC XY: 1593 AN XY: 74348

African (AFR) AF: 0.0113 AC: 469 AN: 41432

American (AMR) AF: 0.0210 AC: 320 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4822

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10598

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0318 AC: 2163 AN: 67992

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0255 Hom.: 4

Bravo AF: 0.0222

Asia WGS AF: 0.00434 AC: 15 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.36
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism

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: rs10189889; hg19: chr2-125445464;