16-50291459-G-C

Variant names:

• chr16-50291459-G-C
• rs7202127
• NM_001114.5:c.376-277G>C

Variant summary

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

The NM_001114.5(ADCY7):​c.376-277G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,204 control chromosomes in the GnomAD database, including 3,841 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 0.22 (3841 hom., cov: 34)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.376-277G>C		intron_variant	Intron 3 of 25	ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.376-277G>C		intron_variant	Intron 3 of 25		NM_001114.5	ENSP00000501053.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33092 AN: 152086 Hom.: 3843 Cov.: 34

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.218 AC: 33106 AN: 152204 Hom.: 3841 Cov.: 34 AF XY: 0.213 AC XY: 15833 AN XY: 74422

African (AFR) AF: 0.194 AC: 8066 AN: 41534

American (AMR) AF: 0.194 AC: 2968 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.114 AC: 550 AN: 4832

European-Finnish (FIN) AF: 0.220 AC: 2331 AN: 10614

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17477 AN: 67960

Other (OTH) AF: 0.246 AC: 520 AN: 2114

Alfa AF: 0.229 Hom.: 522

Bravo AF: 0.214

Asia WGS AF: 0.0690 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7202127; hg19: chr16-50325370;