16-50294615-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114.5(ADCY7):​c.837-25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000966 in 931,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.837-25C>G		intron_variant	Intron 6 of 25	ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.837-25C>G		intron_variant	Intron 6 of 25		NM_001114.5	ENSP00000501053.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000966 AC: 9 AN: 931576 Hom.: 0 Cov.: 14 AF XY: 0.00000834 AC XY: 4 AN XY: 479552

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23590

American (AMR) AF: 0.00 AC: 0 AN: 38644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21396

East Asian (EAS) AF: 0.00 AC: 0 AN: 37552

South Asian (SAS) AF: 0.00 AC: 0 AN: 73748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.0000140 AC: 9 AN: 641064

Other (OTH) AF: 0.00 AC: 0 AN: 42594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-0.95

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: rs2302717; hg19: chr16-50328526;