rs17289102

Positions:

• chr16-50308747-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001114.5(ADCY7):​c.2016C>T​(p.Ala672=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,612,688 control chromosomes in the GnomAD database, including 46,036 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 0.18 (3117 hom., cov: 34)
  • Exomes 𝑓: 0.23 (42919 hom.)
• Consequence: ADCY7 NM_001114.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY7	NM_001114.5	c.2016C>T	p.Ala672=	synonymous_variant	17/26	ENST00000673801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY7	ENST00000673801.1	c.2016C>T	p.Ala672=	synonymous_variant	17/26		NM_001114.5	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27247 AN: 152142 Hom.: 3121 Cov.: 34

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.195 AC: 48738 AN: 249846 Hom.: 6018 AF XY: 0.204 AC XY: 27629 AN XY: 135158

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.00332

Gnomad SAS exome AF: 0.167

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.233 AC: 340899 AN: 1460428 Hom.: 42919 Cov.: 35 AF XY: 0.234 AC XY: 169916 AN XY: 726532

Gnomad4 AFR exome AF: 0.0547

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.00585

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.179 AC: 27235 AN: 152260 Hom.: 3117 Cov.: 34 AF XY: 0.178 AC XY: 13238 AN XY: 74454

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.200

Alfa AF: 0.241 Hom.: 10002

Bravo AF: 0.165

Asia WGS AF: 0.0720 AC: 249 AN: 3478

EpiCase AF: 0.259

EpiControl AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17289102; hg19: chr16-50342658; COSMIC: COSV54266924; COSMIC: COSV54266924;