rs1392481

Variant names:

• chr5-7538124-T-C
• rs1392481
• NM_020546.3:c.570+17225T>C

Variant summary

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

The NM_020546.3(ADCY2):​c.570+17225T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,294 control chromosomes in the GnomAD database, including 450 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 0.073 (450 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27
• Publications: 4 publications found

Genes affected

ADCY2 (HGNC:233): (adenylate cyclase 2) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020546.3. 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
	ADCY2	NM_020546.3	MANE Select	c.570+17225T>C		intron	N/A	NP_065433.2	Q08462-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.570+17225T>C		intron	N/A	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.570+17225T>C		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.570+17225T>C		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11020 AN: 152176 Hom.: 447 Cov.: 33

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0726 AC: 11053 AN: 152294 Hom.: 450 Cov.: 33 AF XY: 0.0741 AC XY: 5521 AN XY: 74468

African (AFR) AF: 0.0518 AC: 2153 AN: 41564

American (AMR) AF: 0.0717 AC: 1096 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3472

East Asian (EAS) AF: 0.189 AC: 979 AN: 5180

South Asian (SAS) AF: 0.100 AC: 483 AN: 4826

European-Finnish (FIN) AF: 0.0968 AC: 1028 AN: 10622

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4853 AN: 68018

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.0745 Hom.: 876

Bravo AF: 0.0708

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.091
DANN	Benign	0.41
PhyloP100		-4.3
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: rs1392481; hg19: chr5-7538237;