Variant 7-45574559-C-CGCGGCGGAGGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_021116.4(ADCY1):c.32_43dup(p.Gly11_Gly14dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 977,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ADCY1
NM_021116.4 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_021116.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCY1	NM_021116.4 linkuse as main transcript	c.32_43dup	p.Gly11_Gly14dup	inframe_insertion	1/20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 linkuse as main transcript	c.32_43dup	p.Gly11_Gly14dup	inframe_insertion	1/19		XP_005249641.1
ADCY1	XM_005249585.3 linkuse as main transcript	c.32_43dup	p.Gly11_Gly14dup	inframe_insertion	1/9		XP_005249642.1
ADCY1	NM_001281768.2 linkuse as main transcript	c.-330-314_-330-303dup		intron_variant			NP_001268697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12 linkuse as main transcript	c.32_43dup	p.Gly11_Gly14dup	inframe_insertion	1/20	1	NM_021116.4	ENSP00000297323	P1
ADCY1	ENST00000432715.5 linkuse as main transcript	c.-330-314_-330-303dup		intron_variant		2		ENSP00000392721

Frequencies

GnomAD3 genomes

AF:

0.0000769

AC:

AN:

143096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00125

Gnomad SAS

AF:

0.000427

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000312

AC:

AN:

833890

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

385172

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00110

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000146

GnomAD4 genome

AF:

0.0000699

AC:

AN:

143132

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

69580

show subpopulations

Gnomad4 AFR

AF:

0.0000502

Gnomad4 AMR

AF:

0.0000687

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00126

Gnomad4 SAS

AF:

0.000214

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 09, 2023

This variant, c.32_43dup, results in the insertion of 4 amino acid(s) of the ADCY1 protein (p.Gly11_Gly14dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ADCY1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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