chr14-24330152-C-A

Variant names:

• chr14-24330152-C-A
• rs10483285
• NM_001198568.2:c.1058+16G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198568.2. 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
	ADCY4	NM_001198568.2	MANE Select	c.1058+16G>T		intron	N/A	NP_001185497.1
	ADCY4	NM_001198592.2		c.1058+16G>T		intron	N/A	NP_001185521.1
	ADCY4	NM_139247.4		c.1058+16G>T		intron	N/A	NP_640340.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY4	ENST00000418030.7	TSL:1 MANE Select	c.1058+16G>T		intron	N/A	ENSP00000393177.2
	ADCY4	ENST00000554068.6	TSL:1	c.1058+16G>T		intron	N/A	ENSP00000452250.2
	ADCY4	ENST00000554781.5	TSL:1	n.1090+16G>T		intron	N/A	ENSP00000450477.1

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

GnomAD2 exomes AF: 0.0651 AC: 16300 AN: 250214 AF XY: 0.0673

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 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

African (AFR) AF: 0.0455 AC: 1518 AN: 33388

American (AMR) AF: 0.0352 AC: 1570 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 1805 AN: 26092

East Asian (EAS) AF: 0.105 AC: 4153 AN: 39530

South Asian (SAS) AF: 0.0890 AC: 7667 AN: 86172

European-Finnish (FIN) AF: 0.0508 AC: 2697 AN: 53102

Middle Eastern (MID) AF: 0.0551 AC: 315 AN: 5718

European-Non Finnish (NFE) AF: 0.0589 AC: 65259 AN: 1108158

Other (OTH) AF: 0.0624 AC: 3751 AN: 60134

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

African (AFR) AF: 0.0467 AC: 1941 AN: 41558

American (AMR) AF: 0.0337 AC: 515 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5184

South Asian (SAS) AF: 0.0884 AC: 427 AN: 4830

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4155 AN: 68024

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0629 Hom.: 208

Bravo AF: 0.0559

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.50
DANN	Benign	0.79
PhyloP100		-1.9
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: rs10483285; hg19: chr14-24799358; COSMIC: COSV60254567; COSMIC: COSV60254567;