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7-45574747-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_021116.4(ADCY1):c.204C>T(p.Leu68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,433,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0490
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-45574747-C-T is Benign according to our data. Variant chr7-45574747-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.049 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADCY1NM_021116.4 linkuse as main transcriptc.204C>T p.Leu68= synonymous_variant 1/20 ENST00000297323.12
ADCY1XM_005249584.4 linkuse as main transcriptc.204C>T p.Leu68= synonymous_variant 1/19
ADCY1XM_005249585.3 linkuse as main transcriptc.204C>T p.Leu68= synonymous_variant 1/9
ADCY1NM_001281768.2 linkuse as main transcriptc.-330-142C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADCY1ENST00000297323.12 linkuse as main transcriptc.204C>T p.Leu68= synonymous_variant 1/201 NM_021116.4 P1
ADCY1ENST00000432715.5 linkuse as main transcriptc.-330-142C>T intron_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000178
AC:
27
AN:
151514
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000460
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:
0.000251
Gnomad OTH
AF:
0.000482
GnomAD3 exomes
AF:
0.000470
AC:
20
AN:
42542
Hom.:
0
AF XY:
0.000439
AC XY:
11
AN XY:
25056
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00223
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:
0.000399
Gnomad OTH exome
AF:
0.000831
GnomAD4 exome
AF:
0.000296
AC:
379
AN:
1281802
Hom.:
1
Cov.:
30
AF XY:
0.000281
AC XY:
177
AN XY:
630234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000406
Gnomad4 AMR exome
AF:
0.00135
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000795
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000320
Gnomad4 OTH exome
AF:
0.000398
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000178
AC:
27
AN:
151620
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74080
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000459
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000251
Gnomad4 OTH
AF:
0.000477
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.000310

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingInvitaeJun 03, 2023- -
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 22, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
6.4
Dann
Benign
0.97

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.

Other links and lift over

dbSNP: rs531991756; hg19: chr7-45614346; API