dbSNP rs12754: ADCY1:c.*7600T>G (chr7-45721595-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021116.4(ADCY1):c.*7600T>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 0.188 in 398,116 control chromosomes in the GnomAD database, including 8,384 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 0.22 ( 4484 hom., cov: 32)

Exomes 𝑓: 0.17 ( 3900 hom. )

Consequence

ADCY1
NM_021116.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.02

Publications

12 publications found

Variant links:

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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
autosomal recessive nonsyndromic hearing loss 44
Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ADCY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4 link	c.*7600T>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.*7895T>G		3_prime_UTR_variant	Exon 19 of 19		XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12 link	c.*7600T>G		3_prime_UTR_variant	Exon 20 of 20	1	NM_021116.4	ENSP00000297323.7		Q08828

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33496

AN:

151944

Hom.:

4474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.167

AC:

41181

AN:

246054

Hom.:

3900

Cov.:

AF XY:

0.167

AC XY:

20771

AN XY:

124676

show subpopulations

African (AFR)

AF:

0.376

AC:

2694

AN:

7172

American (AMR)

AF:

0.138

AC:

1023

AN:

7430

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

1997

AN:

9236

East Asian (EAS)

AF:

0.0642

AC:

1470

AN:

22886

South Asian (SAS)

AF:

0.0449

AC:

131

AN:

2920

European-Finnish (FIN)

AF:

0.135

AC:

2809

AN:

20798

Middle Eastern (MID)

AF:

0.189

AC:

245

AN:

1296

European-Non Finnish (NFE)

AF:

0.176

AC:

27839

AN:

157962

Other (OTH)

AF:

0.182

AC:

2973

AN:

16354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1806

3612

5419

7225

9031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.220

AC:

33528

AN:

152062

Hom.:

4484

Cov.:

AF XY:

0.215

AC XY:

16019

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.382

AC:

15796

AN:

41386

American (AMR)

AF:

0.147

AC:

2249

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

732

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

526

AN:

5182

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4824

European-Finnish (FIN)

AF:

0.138

AC:

1460

AN:

10590

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11782

AN:

68004

Other (OTH)

AF:

0.224

AC:

473

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1249

2498

3747

4996

6245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.199

Hom.:

2557

Bravo

AF:

0.234

Asia WGS

AF:

0.101

AC:

355

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

0.11

(source)

DANN

Benign

0.70

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs12754

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over