rs10198275

Variant names:

• chr2-24907673-A-C
• rs10198275
• NM_004036.5:c.675+10640T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-24907673-A-C
• chr2-24907673-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004036.5(ADCY3):​c.675+10640T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,020 control chromosomes in the GnomAD database, including 22,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22856 hom., cov: 31)
• Consequence: ADCY3 NM_004036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 24 publications found

Genes affected

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ADCY3 Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	NM_004036.5	MANE Select	c.675+10640T>G		intron	N/A	NP_004027.2
	ADCY3	NM_001377128.1		c.675+10640T>G		intron	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.675+10640T>G		intron	N/A	NP_001307542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.675+10640T>G		intron	N/A	ENSP00000505261.1
	ADCY3	ENST00000405392.6	TSL:1	c.675+10640T>G		intron	N/A	ENSP00000384484.2
	ADCY3	ENST00000260600.9	TSL:1	c.675+10640T>G		intron	N/A	ENSP00000260600.5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79201 AN: 151902 Hom.: 22814 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79286 AN: 152020 Hom.: 22856 Cov.: 31 AF XY: 0.514 AC XY: 38184 AN XY: 74288

African (AFR) AF: 0.784 AC: 32508 AN: 41478

American (AMR) AF: 0.375 AC: 5715 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2171 AN: 5158

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 4019 AN: 10554

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29766 AN: 67968

Other (OTH) AF: 0.488 AC: 1031 AN: 2112

Alfa AF: 0.446 Hom.: 7514

Bravo AF: 0.530

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.37
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10198275; hg19: chr2-25130542;