Genetic Variant NM_001114.5:c.2016C>T (chr16-50308747-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001114.5(ADCY7):c.2016C>T(p.Ala672Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,612,688 control chromosomes in the GnomAD database, including 46,036 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 0.18 ( 3117 hom., cov: 34)

Exomes 𝑓: 0.23 ( 42919 hom. )

Consequence

ADCY7
NM_001114.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

11 publications found

Variant links:

Genes affected

ADCY7 (HGNC:238): (adenylate cyclase 7) This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

ADCY7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5 link	c.2016C>T	p.Ala672Ala	synonymous_variant	Exon 17 of 26	ENST00000673801.1	NP_001105.1	P51828Q86YI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1 link	c.2016C>T	p.Ala672Ala	synonymous_variant	Exon 17 of 26		NM_001114.5	ENSP00000501053.1		P51828

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27247

AN:

152142

Hom.:

3121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.203

GnomAD2 exomes

AF:

0.195

AC:

48738

AN:

249846

AF XY:

0.204

show subpopulations

Gnomad AFR exome

AF:

0.0500

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.00332

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.233

AC:

340899

AN:

1460428

Hom.:

42919

Cov.:

AF XY:

0.234

AC XY:

169916

AN XY:

726532

show subpopulations

African (AFR)

AF:

0.0547

AC:

1831

AN:

33470

American (AMR)

AF:

0.108

AC:

4849

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8310

AN:

26102

East Asian (EAS)

AF:

0.00585

AC:

232

AN:

39680

South Asian (SAS)

AF:

0.172

AC:

14832

AN:

86222

European-Finnish (FIN)

AF:

0.242

AC:

12673

AN:

52462

Middle Eastern (MID)

AF:

0.295

AC:

1689

AN:

5730

European-Non Finnish (NFE)

AF:

0.255

AC:

283153

AN:

1111718

Other (OTH)

AF:

0.221

AC:

13330

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

14323

28646

42968

57291

71614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9188

18376

27564

36752

45940

<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:

0.179

AC:

27235

AN:

152260

Hom.:

3117

Cov.:

AF XY:

0.178

AC XY:

13238

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0561

AC:

2334

AN:

41586

American (AMR)

AF:

0.141

AC:

2152

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1145

AN:

3470

East Asian (EAS)

AF:

0.00579

AC:

AN:

5180

South Asian (SAS)

AF:

0.155

AC:

747

AN:

4830

European-Finnish (FIN)

AF:

0.253

AC:

2684

AN:

10608

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17425

AN:

67970

Other (OTH)

AF:

0.200

AC:

422

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1149

2298

3448

4597

5746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.232

Hom.:

18063

Bravo

AF:

0.165

Asia WGS

AF:

0.0720

AC:

249

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.1

(source)

DANN

Benign

0.77

PhyloP100

-2.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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