Variant NM_021116.4:c.1307+14G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_021116.4(ADCY1):c.1307+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,579,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

ADCY1
NM_021116.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.884

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 Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 7-45657899-G-A is Benign according to our data. Variant chr7-45657899-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 506197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ADCY1	NM_021116.4 link	c.1307+14G>A	intron_variant	Intron 6 of 19	ENST00000297323.12	NP_066939.1
ADCY1	NM_001281768.2 link	c.632+14G>A	intron_variant	Intron 7 of 9		NP_001268697.1
ADCY1	XM_005249584.4 link	c.1307+14G>A	intron_variant	Intron 6 of 18		XP_005249641.1
ADCY1	XM_005249585.3 link	c.1307+14G>A	intron_variant	Intron 6 of 8		XP_005249642.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCY1	ENST00000297323.12 link	c.1307+14G>A	intron_variant	Intron 6 of 19	1	NM_021116.4	ENSP00000297323.7	Q08828
ADCY1	ENST00000432715.5 link	c.632+14G>A	intron_variant	Intron 7 of 9	2		ENSP00000392721.1	C9J1J0
ADCY1	ENST00000621543.1 link	c.632+14G>A	intron_variant	Intron 6 of 8	5		ENSP00000479770.1	C9J1J0
ADCY1	ENST00000646653.1 link	n.248+14G>A	intron_variant	Intron 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000922

AC:

AN:

217002

Hom.:

AF XY:

0.00000857

AC XY:

AN XY:

116702

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1426846

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707288

show subpopulations

Gnomad4 AFR exome

AF:

0.000395

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 27, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.1307+14G>A in intron 6 of ADCY1: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and it is not predicted to impact splicing. It has been identified in 3/21172 Afric an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org). ACMG/AMP Criteria applied: BP4, BP7. -

not provided

Benign:1

Jan 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

DANN

Benign

0.32

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