2-24894108-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY3	NM_004036.5	c.676-21389G>A		intron_variant	Intron 2 of 21	ENST00000679454.1	NP_004027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY3	ENST00000679454.1	c.676-21389G>A		intron_variant	Intron 2 of 21		NM_004036.5	ENSP00000505261.1
ADCY3	ENST00000405392.6	c.676-21389G>A		intron_variant	Intron 1 of 20	1		ENSP00000384484.2
ADCY3	ENST00000260600.9	c.676-21389G>A		intron_variant	Intron 1 of 20	1		ENSP00000260600.5
ADCY3	ENST00000435135.5	c.675+24205G>A		intron_variant	Intron 2 of 7	5		ENSP00000389799.1

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

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.410

Alfa AF: 0.345 Hom.: 12480

Bravo AF: 0.477

Asia WGS AF: 0.390 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs7586879; hg19: chr2-25116977;