chr7-45718248-A-G

Position:

• chr7-45718248-A-G

Variant summary

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

The NM_021116.4(ADCY1):​c.*4253A>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 0.0737 in 152,362 control chromosomes in the GnomAD database, including 459 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 0.074 (457 hom., cov: 33)
  • Exomes 𝑓: 0.075 (2 hom.)
• Consequence: ADCY1 NM_021116.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.*4253A>G		3_prime_UTR_variant	20/20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4	c.*4548A>G		3_prime_UTR_variant	19/19		XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12	c.*4253A>G		3_prime_UTR_variant	20/20	1	NM_021116.4	ENSP00000297323	P1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11208 AN: 152164 Hom.: 456 Cov.: 33

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0750 AC: 6 AN: 80 Hom.: 2 Cov.: 0 AF XY: 0.0357 AC XY: 2 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0737 AC: 11217 AN: 152282 Hom.: 457 Cov.: 33 AF XY: 0.0743 AC XY: 5531 AN XY: 74454

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0713 Hom.: 389

Bravo AF: 0.0714

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.39

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: rs10225980; hg19: chr7-45757847;