chr16-50294095-G-A

Variant names:

• chr16-50294095-G-A
• rs1540624
• NM_001114.5:c.837-545G>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.837-545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,056 control chromosomes in the GnomAD database, including 18,077 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 0.48 (18077 hom., cov: 32)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 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.837-545G>A		intron	N/A	NP_001105.1
	ADCY7	NM_001286057.2		c.837-545G>A		intron	N/A	NP_001272986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY7	ENST00000673801.1	MANE Select	c.837-545G>A		intron	N/A	ENSP00000501053.1
	ADCY7	ENST00000254235.7	TSL:1	c.837-545G>A		intron	N/A	ENSP00000254235.3
	ADCY7	ENST00000567277.6	TSL:1	n.837-545G>A		intron	N/A	ENSP00000455670.2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73178 AN: 151938 Hom.: 18060 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.482 AC: 73242 AN: 152056 Hom.: 18077 Cov.: 32 AF XY: 0.470 AC XY: 34939 AN XY: 74320

African (AFR) AF: 0.438 AC: 18155 AN: 41476

American (AMR) AF: 0.459 AC: 7015 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2045 AN: 3472

East Asian (EAS) AF: 0.181 AC: 934 AN: 5162

South Asian (SAS) AF: 0.379 AC: 1826 AN: 4818

European-Finnish (FIN) AF: 0.407 AC: 4305 AN: 10578

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37185 AN: 67956

Other (OTH) AF: 0.482 AC: 1017 AN: 2112

Alfa AF: 0.523 Hom.: 2624

Bravo AF: 0.481

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.67
PhyloP100		-0.38
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: rs1540624; hg19: chr16-50328006;