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GeneBe

7-45574801-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021116.4(ADCY1):c.258C>G(p.Pro86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,571,524 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 10 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.149
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 -17 ACMG points.

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=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-45574801-C-G is Benign according to our data. Variant chr7-45574801-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-45574801-C-G is described in Lovd as [Likely_benign].
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=0.149 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADCY1NM_021116.4 linkuse as main transcriptc.258C>G p.Pro86= synonymous_variant 1/20 ENST00000297323.12
ADCY1XM_005249584.4 linkuse as main transcriptc.258C>G p.Pro86= synonymous_variant 1/19
ADCY1XM_005249585.3 linkuse as main transcriptc.258C>G p.Pro86= synonymous_variant 1/9
ADCY1NM_001281768.2 linkuse as main transcriptc.-330-88C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADCY1ENST00000297323.12 linkuse as main transcriptc.258C>G p.Pro86= synonymous_variant 1/201 NM_021116.4 P1
ADCY1ENST00000432715.5 linkuse as main transcriptc.-330-88C>G intron_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000687
AC:
104
AN:
151470
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.000869
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00456
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00641
Gnomad NFE
AF:
0.000724
Gnomad OTH
AF:
0.000481
GnomAD3 exomes
AF:
0.00152
AC:
285
AN:
187354
Hom.:
4
AF XY:
0.00181
AC XY:
191
AN XY:
105400
show subpopulations
Gnomad AFR exome
AF:
0.000130
Gnomad AMR exome
AF:
0.000380
Gnomad ASJ exome
AF:
0.00183
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00743
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000688
Gnomad OTH exome
AF:
0.00244
GnomAD4 exome
AF:
0.000842
AC:
1196
AN:
1419948
Hom.:
10
Cov.:
31
AF XY:
0.00106
AC XY:
747
AN XY:
705336
show subpopulations
Gnomad4 AFR exome
AF:
0.000306
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00177
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00675
Gnomad4 FIN exome
AF:
0.0000208
Gnomad4 NFE exome
AF:
0.000415
Gnomad4 OTH exome
AF:
0.00125
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000686
AC:
104
AN:
151576
Hom.:
1
Cov.:
32
AF XY:
0.000689
AC XY:
51
AN XY:
74066
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.000869
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00456
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000724
Gnomad4 OTH
AF:
0.000476
Alfa
AF:
0.00110
Hom.:
2
Bravo
AF:
0.000706

ClinVar

Significance: Benign/Likely 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 submitterclinical testingInvitaeJan 25, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 27, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
12
Dann
Benign
0.73

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: rs200597993; hg19: chr7-45614400; API