Variant rs1042009 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021116.4(ADCY1):c.1605+2158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,535,732 control chromosomes in the GnomAD database, including 332,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.55 ( 26095 hom., cov: 31)

Exomes 𝑓: 0.66 ( 306062 hom. )

Consequence

ADCY1
NM_021116.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.337

Variant links:

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADCY1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-45664372-G-A is Benign according to our data. Variant chr7-45664372-G-A is described in ClinVar as [Benign]. Clinvar id is 1280820.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCY1	NM_021116.4 linkuse as main transcript	c.1605+2158G>A		intron_variant		ENST00000297323.12	NP_066939.1
ADCY1	NM_001281768.2 linkuse as main transcript	c.1014G>A	p.Thr338=	synonymous_variant	10/10		NP_001268697.1
ADCY1	XM_005249585.3 linkuse as main transcript	c.1689G>A	p.Thr563=	synonymous_variant	9/9		XP_005249642.1
ADCY1	XM_005249584.4 linkuse as main transcript	c.1605+2158G>A		intron_variant			XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADCY1	ENST00000297323.12 linkuse as main transcript	c.1605+2158G>A		intron_variant		1	NM_021116.4	ENSP00000297323	P1
ADCY1	ENST00000432715.5 linkuse as main transcript	c.1014G>A	p.Thr338=	synonymous_variant	10/10	2		ENSP00000392721
ADCY1	ENST00000621543.1 linkuse as main transcript	c.1014G>A	p.Thr338=	synonymous_variant	9/9	5		ENSP00000479770
ADCY1	ENST00000646653.1 linkuse as main transcript	n.546+2158G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83044

AN:

151908

Hom.:

26089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.631

AC:

86273

AN:

136700

Hom.:

28580

AF XY:

0.642

AC XY:

47702

AN XY:

74342

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.654

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.719

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.659

AC:

911446

AN:

1383706

Hom.:

306062

Cov.:

AF XY:

0.662

AC XY:

452105

AN XY:

682780

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.646

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.716

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.677

Gnomad4 OTH exome

AF:

0.634

GnomAD4 genome

AF:

0.546

AC:

83077

AN:

152026

Hom.:

26095

Cov.:

AF XY:

0.552

AC XY:

41011

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.638

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.327

Gnomad4 SAS

AF:

0.701

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.654

Hom.:

78332

Bravo

AF:

0.514

Asia WGS

AF:

0.526

AC:

1826

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.42

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