Genetic Variant ADCY7:c.837-25C>T (chr16-50294615-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001114.5(ADCY7):c.837-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,083,388 control chromosomes in the GnomAD database, including 65,552 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 0.25 ( 6168 hom., cov: 32)

Exomes 𝑓: 0.29 ( 59384 hom. )

Consequence

ADCY7
NM_001114.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.948

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5 link	c.837-25C>T		intron_variant	Intron 6 of 25	ENST00000673801.1	NP_001105.1	P51828Q86YI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1 link	c.837-25C>T		intron_variant	Intron 6 of 25		NM_001114.5	ENSP00000501053.1		P51828

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38626

AN:

151932

Hom.:

6171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.334

AC:

67633

AN:

202414

AF XY:

0.331

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.835

Gnomad FIN exome

AF:

0.375

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.285

AC:

265880

AN:

931338

Hom.:

59384

Cov.:

AF XY:

0.289

AC XY:

138518

AN XY:

479394

show subpopulations

African (AFR)

AF:

0.243

AC:

5725

AN:

23584

American (AMR)

AF:

0.440

AC:

16997

AN:

38624

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

3461

AN:

21392

East Asian (EAS)

AF:

0.800

AC:

30017

AN:

37544

South Asian (SAS)

AF:

0.490

AC:

36106

AN:

73728

European-Finnish (FIN)

AF:

0.368

AC:

17875

AN:

48544

Middle Eastern (MID)

AF:

0.221

AC:

975

AN:

4404

European-Non Finnish (NFE)

AF:

0.222

AC:

142210

AN:

640932

Other (OTH)

AF:

0.294

AC:

12514

AN:

42586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.626

Heterozygous variant carriers

4343

8686

13028

17371

21714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4008

8016

12024

16032

20040

<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:

0.254

AC:

38645

AN:

152050

Hom.:

6168

Cov.:

AF XY:

0.271

AC XY:

20151

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.219

AC:

9070

AN:

41478

American (AMR)

AF:

0.324

AC:

4957

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

565

AN:

3472

East Asian (EAS)

AF:

0.815

AC:

4196

AN:

5148

South Asian (SAS)

AF:

0.501

AC:

2411

AN:

4816

European-Finnish (FIN)

AF:

0.367

AC:

3876

AN:

10568

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12923

AN:

67960

Other (OTH)

AF:

0.248

AC:

524

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1319

2638

3957

5276

6595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.205

Hom.:

1137

Bravo

AF:

0.252

Asia WGS

AF:

0.625

AC:

2173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.63

PhyloP100

-0.95

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