Variant 12-48771622-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY6	NM_015270.5 linkuse as main transcript	c.3051+88G>A		intron_variant		ENST00000357869.8	NP_056085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY6	ENST00000357869.8 linkuse as main transcript	c.3051+88G>A		intron_variant		2	NM_015270.5	ENSP00000350536	P1	O43306-1

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

GnomAD3 exomes

AF:

0.0206

AC:

4929

AN:

239488

Hom.:

575

AF XY:

0.0146

AC XY:

1904

AN XY:

130238

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 SAS exome

AF:

0.000426

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

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.00507

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000598

Gnomad4 FIN exome

AF:

0.0000231

Gnomad4 NFE exome

AF:

0.000576

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0728

AC:

11073

AN:

152148

Hom.:

1337

Cov.:

AF XY:

0.0703

AC XY:

5226

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0486

Hom.:

153

Bravo

AF:

0.0828

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.82

DANN

Benign

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over