16-50294615-C-T

Variant names:

• chr16-50294615-C-T
• rs2302717
• NM_001114.5:c.837-25C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY7	NM_001114.5	MANE Select	c.837-25C>T		intron	N/A	NP_001105.1	P51828
	ADCY7	NM_001286057.2		c.837-25C>T		intron	N/A	NP_001272986.1	F5H4D1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY7	ENST00000673801.1	MANE Select	c.837-25C>T		intron	N/A	ENSP00000501053.1	P51828
	ADCY7	ENST00000254235.7	TSL:1	c.837-25C>T		intron	N/A	ENSP00000254235.3	P51828
	ADCY7	ENST00000567277.6	TSL:1	n.837-25C>T		intron	N/A	ENSP00000455670.2	H3BQ93

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

GnomAD2 exomes AF: 0.334 AC: 67633 AN: 202414 AF XY: 0.331

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 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

African (AFR) AF: 0.243 AC: 5725 AN: 23584

American (AMR) AF: 0.440 AC: 16997 AN: 38624

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3461 AN: 21392

East Asian (EAS) AF: 0.800 AC: 30017 AN: 37544

South Asian (SAS) AF: 0.490 AC: 36106 AN: 73728

European-Finnish (FIN) AF: 0.368 AC: 17875 AN: 48544

Middle Eastern (MID) AF: 0.221 AC: 975 AN: 4404

European-Non Finnish (NFE) AF: 0.222 AC: 142210 AN: 640932

Other (OTH) AF: 0.294 AC: 12514 AN: 42586

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

African (AFR) AF: 0.219 AC: 9070 AN: 41478

American (AMR) AF: 0.324 AC: 4957 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4196 AN: 5148

South Asian (SAS) AF: 0.501 AC: 2411 AN: 4816

European-Finnish (FIN) AF: 0.367 AC: 3876 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12923 AN: 67960

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.205 Hom.: 1137

Bravo AF: 0.252

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.63
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: rs2302717; hg19: chr16-50328526; COSMIC: COSV54265293; COSMIC: COSV54265293;