7-122701095-T-C

Variant names:

• chr7-122701095-T-C
• rs6466832
• NM_017954.11:c.453+35860A>G

Variant summary

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

The NM_017954.11(CADPS2):​c.453+35860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,936 control chromosomes in the GnomAD database, including 34,968 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 0.67 (34968 hom., cov: 31)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 4 publications found

Genes affected

CADPS2 (HGNC:16018): (calcium dependent secretion activator 2) This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS2	NM_017954.11	c.453+35860A>G		intron_variant	Intron 2 of 29	ENST00000449022.7	NP_060424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS2	ENST00000449022.7	c.453+35860A>G		intron_variant	Intron 2 of 29	5	NM_017954.11	ENSP00000398481.2
CADPS2	ENST00000412584.6	c.453+35860A>G		intron_variant	Intron 2 of 27	1		ENSP00000400401.2
CADPS2	ENST00000313070.11	c.135+35860A>G		intron_variant	Intron 2 of 29	5		ENSP00000325581.8

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101904 AN: 151818 Hom.: 34974 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.671 AC: 101928 AN: 151936 Hom.: 34968 Cov.: 31 AF XY: 0.672 AC XY: 49876 AN XY: 74250

African (AFR) AF: 0.509 AC: 21106 AN: 41432

American (AMR) AF: 0.752 AC: 11455 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2574 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4118 AN: 5152

South Asian (SAS) AF: 0.707 AC: 3405 AN: 4816

European-Finnish (FIN) AF: 0.659 AC: 6960 AN: 10560

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49836 AN: 67950

Other (OTH) AF: 0.694 AC: 1464 AN: 2110

Alfa AF: 0.686 Hom.: 11139

Bravo AF: 0.673

Asia WGS AF: 0.735 AC: 2551 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.9
DANN	Benign	0.93
PhyloP100		-0.95
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: rs6466832; hg19: chr7-122341149;