rs17289102

Variant names:

• chr16-50308747-C-T
• rs17289102
• NM_001114.5:c.2016C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001114.5(ADCY7):​c.2016C>T​(p.Ala672Ala) 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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY7	NM_001114.5	MANE Select	c.2016C>T	p.Ala672Ala	synonymous	Exon 17 of 26	NP_001105.1
	ADCY7	NM_001286057.2		c.2016C>T	p.Ala672Ala	synonymous	Exon 17 of 19	NP_001272986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY7	ENST00000673801.1	MANE Select	c.2016C>T	p.Ala672Ala	synonymous	Exon 17 of 26	ENSP00000501053.1
	ADCY7	ENST00000254235.7	TSL:1	c.2016C>T	p.Ala672Ala	synonymous	Exon 16 of 25	ENSP00000254235.3
	ADCY7	ENST00000567277.6	TSL:1	n.*388C>T		non_coding_transcript_exon	Exon 16 of 18	ENSP00000455670.2

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

GnomAD2 exomes AF: 0.195 AC: 48738 AN: 249846 AF XY: 0.204

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 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

African (AFR) AF: 0.0547 AC: 1831 AN: 33470

American (AMR) AF: 0.108 AC: 4849 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8310 AN: 26102

East Asian (EAS) AF: 0.00585 AC: 232 AN: 39680

South Asian (SAS) AF: 0.172 AC: 14832 AN: 86222

European-Finnish (FIN) AF: 0.242 AC: 12673 AN: 52462

Middle Eastern (MID) AF: 0.295 AC: 1689 AN: 5730

European-Non Finnish (NFE) AF: 0.255 AC: 283153 AN: 1111718

Other (OTH) AF: 0.221 AC: 13330 AN: 60346

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

African (AFR) AF: 0.0561 AC: 2334 AN: 41586

American (AMR) AF: 0.141 AC: 2152 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3470

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5180

South Asian (SAS) AF: 0.155 AC: 747 AN: 4830

European-Finnish (FIN) AF: 0.253 AC: 2684 AN: 10608

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17425 AN: 67970

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.232 Hom.: 18063

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.77
PhyloP100		-2.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17289102; hg19: chr16-50342658; COSMIC: COSV54266924; COSMIC: COSV54266924;