NM_004036.5:c.676-21389G>A

Variant names:

• chr2-24894108-C-T
• rs7586879
• NM_004036.5:c.676-21389G>A

Variant summary

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

The NM_004036.5(ADCY3):​c.676-21389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,994 control chromosomes in the GnomAD database, including 19,606 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 0.47 (19606 hom., cov: 32)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 29 publications found

Genes affected

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ADCY3 Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

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 (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. 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
	ADCY3	NM_004036.5	MANE Select	c.676-21389G>A		intron	N/A	NP_004027.2	O60266-1
	ADCY3	NM_001377128.1		c.676-21389G>A		intron	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.676-21389G>A		intron	N/A	NP_001307542.1	A0A0A0MSC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.676-21389G>A		intron	N/A	ENSP00000505261.1	O60266-1
	ADCY3	ENST00000405392.6	TSL:1	c.676-21389G>A		intron	N/A	ENSP00000384484.2	A0A0A0MSC1
	ADCY3	ENST00000260600.9	TSL:1	c.676-21389G>A		intron	N/A	ENSP00000260600.5	O60266-1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70985 AN: 151878 Hom.: 19565 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.468 AC: 71073 AN: 151994 Hom.: 19606 Cov.: 32 AF XY: 0.464 AC XY: 34437 AN XY: 74268

African (AFR) AF: 0.782 AC: 32417 AN: 41458

American (AMR) AF: 0.320 AC: 4877 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5178

South Asian (SAS) AF: 0.430 AC: 2075 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10538

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23708 AN: 67956

Other (OTH) AF: 0.410 AC: 867 AN: 2114

Alfa AF: 0.372 Hom.: 22462

Bravo AF: 0.477

Asia WGS AF: 0.390 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.29
PhyloP100		-3.2
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: rs7586879; hg19: chr2-25116977;