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GeneBe

7-45574777-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021116.4(ADCY1):c.234C>G(p.Ala78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,493,600 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 18 hom., cov: 32)
Exomes 𝑓: 0.015 ( 212 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.386
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-45574777-C-G is Benign according to our data. Variant chr7-45574777-C-G is described in ClinVar as [Benign]. Clinvar id is 1238867.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=0.386 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0149 (20040/1343204) while in subpopulation MID AF= 0.0369 (145/3930). AF 95% confidence interval is 0.032. There are 212 homozygotes in gnomad4_exome. There are 9681 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
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 GnomAd at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADCY1NM_021116.4 linkuse as main transcriptc.234C>G p.Ala78= synonymous_variant 1/20 ENST00000297323.12
ADCY1XM_005249584.4 linkuse as main transcriptc.234C>G p.Ala78= synonymous_variant 1/19
ADCY1XM_005249585.3 linkuse as main transcriptc.234C>G p.Ala78= synonymous_variant 1/9
ADCY1NM_001281768.2 linkuse as main transcriptc.-330-112C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADCY1ENST00000297323.12 linkuse as main transcriptc.234C>G p.Ala78= synonymous_variant 1/201 NM_021116.4 P1
ADCY1ENST00000432715.5 linkuse as main transcriptc.-330-112C>G intron_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1943
AN:
150290
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00278
Gnomad AMI
AF:
0.0100
Gnomad AMR
AF:
0.0145
Gnomad ASJ
AF:
0.0457
Gnomad EAS
AF:
0.000198
Gnomad SAS
AF:
0.00230
Gnomad FIN
AF:
0.0302
Gnomad MID
AF:
0.0461
Gnomad NFE
AF:
0.0158
Gnomad OTH
AF:
0.0219
GnomAD3 exomes
AF:
0.0153
AC:
1452
AN:
95198
Hom.:
19
AF XY:
0.0146
AC XY:
788
AN XY:
54058
show subpopulations
Gnomad AFR exome
AF:
0.00246
Gnomad AMR exome
AF:
0.00940
Gnomad ASJ exome
AF:
0.0460
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00231
Gnomad FIN exome
AF:
0.0268
Gnomad NFE exome
AF:
0.0177
Gnomad OTH exome
AF:
0.0231
GnomAD4 exome
AF:
0.0149
AC:
20040
AN:
1343204
Hom.:
212
Cov.:
31
AF XY:
0.0146
AC XY:
9681
AN XY:
662890
show subpopulations
Gnomad4 AFR exome
AF:
0.00368
Gnomad4 AMR exome
AF:
0.0104
Gnomad4 ASJ exome
AF:
0.0455
Gnomad4 EAS exome
AF:
0.0000322
Gnomad4 SAS exome
AF:
0.00329
Gnomad4 FIN exome
AF:
0.0256
Gnomad4 NFE exome
AF:
0.0153
Gnomad4 OTH exome
AF:
0.0170
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1943
AN:
150396
Hom.:
18
Cov.:
32
AF XY:
0.0132
AC XY:
969
AN XY:
73450
show subpopulations
Gnomad4 AFR
AF:
0.00277
Gnomad4 AMR
AF:
0.0144
Gnomad4 ASJ
AF:
0.0457
Gnomad4 EAS
AF:
0.000199
Gnomad4 SAS
AF:
0.00230
Gnomad4 FIN
AF:
0.0302
Gnomad4 NFE
AF:
0.0158
Gnomad4 OTH
AF:
0.0217
Alfa
AF:
0.0106
Hom.:
7
Bravo
AF:
0.0117

ClinVar

Significance: 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 testingInvitaeDec 28, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 30, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
6.5
Dann
Benign
0.46

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: rs74641956; hg19: chr7-45614376; COSMIC: COSV52040425; COSMIC: COSV52040425; API