rs10249706

Positions:

• chr7-45721752-G-A

Variant summary

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

The NM_021116.4(ADCY1):​c.*7757G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 398,504 control chromosomes in the GnomAD database, including 1,145 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 0.073 (456 hom., cov: 32)
  • Exomes 𝑓: 0.071 (689 hom.)
• Consequence: ADCY1 NM_021116.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY1	NM_021116.4	c.*7757G>A		3_prime_UTR_variant	20/20	ENST00000297323.12
ADCY1	XM_005249584.4	c.*8052G>A		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12	c.*7757G>A		3_prime_UTR_variant	20/20	1	NM_021116.4	P1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11111 AN: 152034 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0712 AC: 17536 AN: 246352 Hom.: 689 Cov.: 0 AF XY: 0.0718 AC XY: 8965 AN XY: 124832

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.0398

Gnomad4 ASJ exome AF: 0.0657

Gnomad4 EAS exome AF: 0.0414

Gnomad4 SAS exome AF: 0.0277

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0734

Gnomad4 OTH exome AF: 0.0733

GnomAD4 genome AF: 0.0731 AC: 11120 AN: 152152 Hom.: 456 Cov.: 32 AF XY: 0.0738 AC XY: 5490 AN XY: 74378

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0730

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0707 Hom.: 554

Bravo AF: 0.0708

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.2
DANN	Benign	0.86

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: rs10249706; hg19: chr7-45761351;