Genetic Variant ADCY7:c.2448+81T>C (chr16-50311867-T-C) – 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.2448+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.69 ( 29295 hom., cov: 20)

Exomes 𝑓: 0.67 ( 250522 hom. )

Consequence

ADCY7
NM_001114.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255

Publications

6 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=-0.78).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114.5. 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
	ADCY7	NM_001114.5	MANE Select	c.2448+81T>C		intron	N/A	NP_001105.1	P51828

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY7	ENST00000673801.1	MANE Select	c.2448+81T>C	intron	N/A	ENSP00000501053.1	P51828
ADCY7	ENST00000254235.7	TSL:1	c.2448+81T>C	intron	N/A	ENSP00000254235.3	P51828
ADCY7	ENST00000394697.7	TSL:5	c.2448+81T>C	intron	N/A	ENSP00000378187.2	P51828

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

90889

AN:

132430

Hom.:

29252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.711

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.700

GnomAD4 exome

AF:

0.672

AC:

772676

AN:

1149810

Hom.:

250522

Cov.:

AF XY:

0.671

AC XY:

390757

AN XY:

582444

show subpopulations

African (AFR)

AF:

0.657

AC:

17618

AN:

26824

American (AMR)

AF:

0.809

AC:

34842

AN:

43088

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

16289

AN:

22998

East Asian (EAS)

AF:

0.571

AC:

16935

AN:

29666

South Asian (SAS)

AF:

0.676

AC:

52376

AN:

77504

European-Finnish (FIN)

AF:

0.580

AC:

26410

AN:

45520

Middle Eastern (MID)

AF:

0.682

AC:

2742

AN:

4020

European-Non Finnish (NFE)

AF:

0.673

AC:

572624

AN:

851478

Other (OTH)

AF:

0.674

AC:

32840

AN:

48712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

13173

26345

39518

52690

65863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13802

27604

41406

55208

69010

<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:

0.686

AC:

91004

AN:

132580

Hom.:

29295

Cov.:

AF XY:

0.685

AC XY:

43616

AN XY:

63644

show subpopulations

African (AFR)

AF:

0.687

AC:

24146

AN:

35152

American (AMR)

AF:

0.785

AC:

10607

AN:

13508

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2335

AN:

3304

East Asian (EAS)

AF:

0.528

AC:

1880

AN:

3562

South Asian (SAS)

AF:

0.700

AC:

2922

AN:

4172

European-Finnish (FIN)

AF:

0.615

AC:

4229

AN:

6882

Middle Eastern (MID)

AF:

0.708

AC:

170

AN:

240

European-Non Finnish (NFE)

AF:

0.678

AC:

42739

AN:

63050

Other (OTH)

AF:

0.702

AC:

1299

AN:

1850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

1477

2953

4430

5906

7383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.640

Hom.:

35501

Bravo

AF:

0.646

Asia WGS

AF:

0.570

AC:

1987

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.26

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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