dbSNP rs10225980: ADCY1:c.*4253A>G (chr7-45718248-A-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.*4253A>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 0.0737 in 152,362 control chromosomes in the GnomAD database, including 459 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 0.074 ( 457 hom., cov: 33)

Exomes 𝑓: 0.075 ( 2 hom. )

Consequence

ADCY1
NM_021116.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

3 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4 link	c.*4253A>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.*4548A>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.*4253A>G		3_prime_UTR_variant	Exon 20 of 20	1	NM_021116.4	ENSP00000297323.7		Q08828

Frequencies

GnomAD3 genomes

AF:

0.0737

AC:

11208

AN:

152164

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0530

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0310

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0752

Gnomad OTH

AF:

0.0612

GnomAD4 exome

AF:

0.0750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0690

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0737

AC:

11217

AN:

152282

Hom.:

457

Cov.:

AF XY:

0.0743

AC XY:

5531

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0790

AC:

3282

AN:

41552

American (AMR)

AF:

0.0529

AC:

810

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3470

East Asian (EAS)

AF:

0.0716

AC:

371

AN:

5178

South Asian (SAS)

AF:

0.0311

AC:

150

AN:

4828

European-Finnish (FIN)

AF:

0.108

AC:

1143

AN:

10608

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0752

AC:

5118

AN:

68018

Other (OTH)

AF:

0.0605

AC:

128

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

538

1076

1615

2153

2691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0717

Hom.:

519

Bravo

AF:

0.0714

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.39

PhyloP100

0.068

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