dbSNP rs10249706: ADCY1:c.*7757G>A (chr7-45721752-G-A) – 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.*7757G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 398,504 control chromosomes in the GnomAD database, including 1,145 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 0.073 ( 456 hom., cov: 32)

Exomes 𝑓: 0.071 ( 689 hom. )

Consequence

ADCY1
NM_021116.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

Publications

6 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=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4 link	c.*7757G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.*8052G>A		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.*7757G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_021116.4	ENSP00000297323.7		Q08828

Frequencies

GnomAD3 genomes

AF:

0.0731

AC:

11111

AN:

152034

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0756

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0524

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0732

Gnomad SAS

AF:

0.0307

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0752

Gnomad OTH

AF:

0.0602

GnomAD4 exome

AF:

0.0712

AC:

17536

AN:

246352

Hom.:

689

Cov.:

AF XY:

0.0718

AC XY:

8965

AN XY:

124832

show subpopulations

African (AFR)

AF:

0.0769

AC:

552

AN:

7182

American (AMR)

AF:

0.0398

AC:

296

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

607

AN:

9240

East Asian (EAS)

AF:

0.0414

AC:

949

AN:

22896

South Asian (SAS)

AF:

0.0277

AC:

AN:

3032

European-Finnish (FIN)

AF:

0.104

AC:

2164

AN:

20828

Middle Eastern (MID)

AF:

0.0634

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.0734

AC:

11602

AN:

158074

Other (OTH)

AF:

0.0733

AC:

1200

AN:

16372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1004

2008

3013

4017

5021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0731

AC:

11120

AN:

152152

Hom.:

456

Cov.:

AF XY:

0.0738

AC XY:

5490

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0756

AC:

3139

AN:

41502

American (AMR)

AF:

0.0523

AC:

799

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

199

AN:

3470

East Asian (EAS)

AF:

0.0730

AC:

378

AN:

5176

South Asian (SAS)

AF:

0.0309

AC:

149

AN:

4820

European-Finnish (FIN)

AF:

0.108

AC:

1144

AN:

10592

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0752

AC:

5115

AN:

67992

Other (OTH)

AF:

0.0596

AC:

126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

521

1042

1564

2085

2606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0711

Hom.:

698

Bravo

AF:

0.0708

Asia WGS

AF:

0.0480

AC:

166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.2

(source)

DANN

Benign

0.86

PhyloP100

0.50

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over