rs2302717

Positions:

• chr16-50294615-C-T

Variant summary

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

The NM_001114.5(ADCY7):​c.837-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,083,388 control chromosomes in the GnomAD database, including 65,552 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 0.25 (6168 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59384 hom.)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

Genes affected

ADCY7 (HGNC:238): (adenylate cyclase 7) This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.837-25C>T		intron_variant		ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.837-25C>T		intron_variant			NM_001114.5	ENSP00000501053	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38626 AN: 151932 Hom.: 6171 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.334 AC: 67633 AN: 202414 Hom.: 15274 AF XY: 0.331 AC XY: 35868 AN XY: 108348

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.835

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.285 AC: 265880 AN: 931338 Hom.: 59384 Cov.: 14 AF XY: 0.289 AC XY: 138518 AN XY: 479394

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.254 AC: 38645 AN: 152050 Hom.: 6168 Cov.: 32 AF XY: 0.271 AC XY: 20151 AN XY: 74306

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.248

Alfa AF: 0.207 Hom.: 645

Bravo AF: 0.252

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.63

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: rs2302717; hg19: chr16-50328526; COSMIC: COSV54265293; COSMIC: COSV54265293;