dbSNP rs3729972: ADCY6:c.3051+88G>A (chr12-48771622-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015270.5(ADCY6):c.3051+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,585,984 control chromosomes in the GnomAD database, including 2,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 1337 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 1237 hom. )

Consequence

ADCY6
NM_015270.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.75

Publications

1 publications found

Variant links:

Genes affected

ADCY6 (HGNC:237): (adenylate cyclase 6) This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

ADCY6 links:

SPMIP11 (HGNC:48628): (sperm microtubule inner protein 11)

SPMIP11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-48771622-C-T is Benign according to our data. Variant chr12-48771622-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY6	NM_015270.5	MANE Select	c.3051+88G>A	intron	N/A	NP_056085.1	O43306-1
ADCY6	NM_001390831.2		c.3051+88G>A	intron	N/A	NP_001377760.1	O43306-1
ADCY6	NM_001412819.1		c.3051+88G>A	intron	N/A	NP_001399748.1	O43306-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY6	ENST00000357869.8	TSL:2 MANE Select	c.3051+88G>A	intron	N/A	ENSP00000350536.4	O43306-1
ADCY6	ENST00000307885.4	TSL:1	c.3051+88G>A	intron	N/A	ENSP00000311405.4	O43306-1
ADCY6	ENST00000960700.1		c.3132+88G>A	intron	N/A	ENSP00000630759.1

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

11045

AN:

152030

Hom.:

1333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.0574

GnomAD2 exomes

AF:

0.0206

AC:

4929

AN:

239488

AF XY:

0.0146

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.00533

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000930

Gnomad OTH exome

AF:

0.00846

GnomAD4 exome

AF:

0.00786

AC:

11267

AN:

1433836

Hom.:

1237

Cov.:

AF XY:

0.00674

AC XY:

4818

AN XY:

714688

show subpopulations

African (AFR)

AF:

0.258

AC:

8527

AN:

33024

American (AMR)

AF:

0.0164

AC:

734

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00507

AC:

132

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.000598

AC:

AN:

85324

European-Finnish (FIN)

AF:

0.0000231

AC:

AN:

43338

Middle Eastern (MID)

AF:

0.0159

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.000576

AC:

632

AN:

1096382

Other (OTH)

AF:

0.0184

AC:

1099

AN:

59720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

523

1046

1568

2091

2614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

246

492

738

984

1230

<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:

0.0728

AC:

11073

AN:

152148

Hom.:

1337

Cov.:

AF XY:

0.0703

AC XY:

5226

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.250

AC:

10342

AN:

41432

American (AMR)

AF:

0.0317

AC:

485

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00119

AC:

AN:

68012

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

424

849

1273

1698

2122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.111

Hom.:

598

Bravo

AF:

0.0828

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.82

(source)

DANN

Benign

0.41

PhyloP100

-2.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over