rs7641344

chr3-123416397-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_183357.3(ADCY5):c.1134+31015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,450,452 control chromosomes in the GnomAD database, including 6,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (1194 hom., cov: 32)
  • Exomes 𝑓: 0.032 (5158 hom.)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.810

Genes affected

ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-123416397-G-A is Benign according to our data. Variant chr3-123416397-G-A is described in ClinVar as [Benign]. Clinvar id is 1260407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY5	NM_183357.3	c.1134+31015C>T		intron_variant		ENST00000462833.6
ADCY5	NM_001378259.1	c.1134+31015C>T		intron_variant
ADCY5	XM_011512359.3	c.135+8258C>T		intron_variant
ADCY5	XM_047447359.1	c.135+8258C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY5	ENST00000462833.6	c.1134+31015C>T		intron_variant		1	NM_183357.3	P1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12452 AN: 152100 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.0713

GnomAD4 exome AF: 0.0321 AC: 41651 AN: 1298234 Hom.: 5158 AF XY: 0.0347 AC XY: 22012 AN XY: 633810

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.00876

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00943

Gnomad4 NFE exome AF: 0.00320

Gnomad4 OTH exome AF: 0.0536

GnomAD4 genome AF: 0.0820 AC: 12480 AN: 152218 Hom.: 1194 Cov.: 32 AF XY: 0.0851 AC XY: 6335 AN XY: 74420

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.00415

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0468 Hom.: 71

Bravo AF: 0.0903

Asia WGS AF: 0.320 AC: 1108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.32
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs7641344; hg19: chr3-123135244;