rs11766192

Positions:

• chr7-45609204-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.790-1175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,112 control chromosomes in the GnomAD database, including 5,437 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 0.24 (5437 hom., cov: 32)
• Consequence: ADCY1 NM_021116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY1	NM_021116.4	c.790-1175C>T		intron_variant		ENST00000297323.12
ADCY1	NM_001281768.2	c.115-1175C>T		intron_variant
ADCY1	XM_005249584.4	c.790-1175C>T		intron_variant
ADCY1	XM_005249585.3	c.790-1175C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12	c.790-1175C>T		intron_variant		1	NM_021116.4	P1
ADCY1	ENST00000432715.5	c.115-1175C>T		intron_variant		2
ADCY1	ENST00000621543.1	c.115-1175C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37102 AN: 151994 Hom.: 5443 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37091 AN: 152112 Hom.: 5437 Cov.: 32 AF XY: 0.251 AC XY: 18637 AN XY: 74352

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.266

Alfa AF: 0.279 Hom.: 9548

Bravo AF: 0.236

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.42

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: rs11766192; hg19: chr7-45648803;