7-45719663-C-T

Position:

• chr7-45719663-C-T

Variant summary

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

The NM_021116.4(ADCY1):​c.*5668C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,098 control chromosomes in the GnomAD database, including 10,591 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 0.34 (10589 hom., cov: 33)
  • Exomes 𝑓: 0.42 (2 hom.)
• Consequence: ADCY1 NM_021116.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY1	NM_021116.4	c.*5668C>T		3_prime_UTR_variant	20/20	ENST00000297323.12
ADCY1	XM_005249584.4	c.*5963C>T		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12	c.*5668C>T		3_prime_UTR_variant	20/20	1	NM_021116.4	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52298 AN: 151970 Hom.: 10585 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.417 AC: 5 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.344 AC: 52318 AN: 152086 Hom.: 10589 Cov.: 33 AF XY: 0.351 AC XY: 26080 AN XY: 74332

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.370

Alfa AF: 0.411 Hom.: 18923

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.65

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: rs2471267; hg19: chr7-45759262;