rs12754

chr7-45721595-T-G

Variant summary

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

The NM_021116.4(ADCY1):c.*7600T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 398,116 control chromosomes in the GnomAD database, including 8,384 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 0.22 (4484 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3900 hom.)
• Consequence: ADCY1 NM_021116.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY1	NM_021116.4	c.*7600T>G		3_prime_UTR_variant	20/20	ENST00000297323.12
ADCY1	XM_005249584.4	c.*7895T>G		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12	c.*7600T>G		3_prime_UTR_variant	20/20	1	NM_021116.4	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33496 AN: 151944 Hom.: 4474 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.167 AC: 41181 AN: 246054 Hom.: 3900 Cov.: 0 AF XY: 0.167 AC XY: 20771 AN XY: 124676

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.220 AC: 33528 AN: 152062 Hom.: 4484 Cov.: 32 AF XY: 0.215 AC XY: 16019 AN XY: 74388

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.224

Alfa AF: 0.189 Hom.: 1535

Bravo AF: 0.234

Asia WGS AF: 0.101 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
Dann	Benign	0.70

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: rs12754; hg19: chr7-45761194;