16-50283905-C-A

Variant names:

• chr16-50283905-C-A
• rs1078151
• NM_001114.5:c.-268-4007C>A

Variant summary

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

The NM_001114.5(ADCY7):​c.-268-4007C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,892 control chromosomes in the GnomAD database, including 7,173 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 0.28 (7173 hom., cov: 32)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.-268-4007C>A		intron_variant	Intron 1 of 25	ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.-268-4007C>A		intron_variant	Intron 1 of 25		NM_001114.5	ENSP00000501053.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42374 AN: 151774 Hom.: 7178 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.279 AC: 42390 AN: 151892 Hom.: 7173 Cov.: 32 AF XY: 0.295 AC XY: 21908 AN XY: 74242

African (AFR) AF: 0.300 AC: 12438 AN: 41418

American (AMR) AF: 0.332 AC: 5069 AN: 15278

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

East Asian (EAS) AF: 0.815 AC: 4185 AN: 5134

South Asian (SAS) AF: 0.510 AC: 2446 AN: 4800

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10556

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13109 AN: 67922

Other (OTH) AF: 0.265 AC: 559 AN: 2106

Alfa AF: 0.219 Hom.: 18432

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.017
DANN	Benign	0.46
PhyloP100		-2.7
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: rs1078151; hg19: chr16-50317816;