Genetic Variant 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: 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)

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.

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.*7600T>G		3_prime_UTR	Exon 20 of 20	NP_066939.1	Q08828

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.*7600T>G		3_prime_UTR	Exon 20 of 20	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

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over