rs11766192

Variant names:

• chr7-45609204-C-T
• rs11766192
• NM_021116.4:c.790-1175C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ADCY1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 44

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	NM_021116.4	MANE Select	c.790-1175C>T		intron	N/A	NP_066939.1	Q08828
	ADCY1	NM_001281768.2		c.115-1175C>T		intron	N/A	NP_001268697.1	C9J1J0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.790-1175C>T		intron	N/A	ENSP00000297323.7	Q08828
	ADCY1	ENST00000920696.1		c.640-1175C>T		intron	N/A	ENSP00000590755.1
	ADCY1	ENST00000432715.5	TSL:2	c.115-1175C>T		intron	N/A	ENSP00000392721.1	C9J1J0

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

African (AFR) AF: 0.0808 AC: 3357 AN: 41524

American (AMR) AF: 0.315 AC: 4822 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2468 AN: 5144

South Asian (SAS) AF: 0.316 AC: 1520 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3533 AN: 10576

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19347 AN: 67976

Other (OTH) AF: 0.266 AC: 562 AN: 2114

Alfa AF: 0.272 Hom.: 22275

Bravo AF: 0.236

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.42
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11766192; hg19: chr7-45648803;