rs10483285

chr14-24330152-C-Achr14-24330152-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198568.2(ADCY4):c.1058+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 1,609,230 control chromosomes in the GnomAD database, including 3,272 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 0.057 (278 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2994 hom.)
• Consequence: ADCY4 NM_001198568.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

ADCY4 (HGNC:235): (adenylate cyclase 4) 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). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY4	NM_001198568.2	c.1058+16G>T		intron_variant		ENST00000418030.7
ADCY4	NM_001198592.2	c.1058+16G>T		intron_variant
ADCY4	NM_139247.4	c.1058+16G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY4	ENST00000418030.7	c.1058+16G>T		intron_variant		1	NM_001198568.2	P1

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8704 AN: 152172 Hom.: 278 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0507

GnomAD3 exomes AF: 0.0651 AC: 16300 AN: 250214 Hom.: 693 AF XY: 0.0673 AC XY: 9099 AN XY: 135188

Gnomad AFR exome AF: 0.0481

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0710

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.0878

Gnomad FIN exome AF: 0.0503

Gnomad NFE exome AF: 0.0605

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0609 AC: 88735 AN: 1456940 Hom.: 2994 Cov.: 35 AF XY: 0.0622 AC XY: 45049 AN XY: 723722

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.0352

Gnomad4 ASJ exome AF: 0.0692

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0890

Gnomad4 FIN exome AF: 0.0508

Gnomad4 NFE exome AF: 0.0589

Gnomad4 OTH exome AF: 0.0624

GnomAD4 genome AF: 0.0572 AC: 8710 AN: 152290 Hom.: 278 Cov.: 32 AF XY: 0.0578 AC XY: 4307 AN XY: 74486

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0611

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0634 Hom.: 194

Bravo AF: 0.0559

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.50
Dann	Benign	0.79

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: rs10483285; hg19: chr14-24799358; COSMIC: COSV60254567; COSMIC: COSV60254567;