rs2461127

chr7-45718207-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.*4212G>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 0.347 in 152,240 control chromosomes in the GnomAD database, including 10,721 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 0.35 (10713 hom., cov: 32)
  • Exomes 𝑓: 0.41 (8 hom.)
• Consequence: ADCY1 NM_021116.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

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 (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY1	NM_021116.4	c.*4212G>A		3_prime_UTR_variant	20/20	ENST00000297323.12
ADCY1	XM_005249584.4	c.*4507G>A		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12	c.*4212G>A		3_prime_UTR_variant	20/20	1	NM_021116.4	P1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52766 AN: 152032 Hom.: 10710 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.413 AC: 38 AN: 92 Hom.: 8 Cov.: 0 AF XY: 0.382 AC XY: 26 AN XY: 68

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.347 AC: 52786 AN: 152148 Hom.: 10713 Cov.: 32 AF XY: 0.354 AC XY: 26325 AN XY: 74366

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.374

Alfa AF: 0.405 Hom.: 12528

Bravo AF: 0.329

Asia WGS AF: 0.510 AC: 1771 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	0.57
Dann	Benign	0.45

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: rs2461127; hg19: chr7-45757806;