1-167894468-G-A

Variant names:

• chr1-167894468-G-A
• rs437846
• NM_018417.6:c.740-527C>T

Variant summary

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

The NM_018417.6(ADCY10):​c.740-527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,028 control chromosomes in the GnomAD database, including 3,689 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 0.22 (3689 hom., cov: 31)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 4 publications found

Genes affected

ADCY10 (HGNC:21285): (adenylate cyclase 10) The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patients with absorptive hypercalciuria. Alternatively spliced transcript variants encoding different isoforms have been observed. There is a pseudogene of this gene on chromosome 6. [provided by RefSeq, Jul 2014]

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018417.6. 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
	ADCY10	NM_018417.6	MANE Select	c.740-527C>T		intron	N/A	NP_060887.2
	ADCY10	NM_001297772.2		c.464-527C>T		intron	N/A	NP_001284701.1
	ADCY10	NM_001167749.3		c.281-527C>T		intron	N/A	NP_001161221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.740-527C>T		intron	N/A	ENSP00000356825.4
	ADCY10	ENST00000367848.1	TSL:1	c.464-527C>T		intron	N/A	ENSP00000356822.1
	ADCY10	ENST00000545172.5	TSL:2	c.281-527C>T		intron	N/A	ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33167 AN: 151910 Hom.: 3685 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.218 AC: 33201 AN: 152028 Hom.: 3689 Cov.: 31 AF XY: 0.218 AC XY: 16227 AN XY: 74328

African (AFR) AF: 0.219 AC: 9096 AN: 41472

American (AMR) AF: 0.268 AC: 4086 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.171 AC: 882 AN: 5154

South Asian (SAS) AF: 0.157 AC: 753 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2121 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14538 AN: 67974

Other (OTH) AF: 0.224 AC: 474 AN: 2114

Alfa AF: 0.217 Hom.: 15525

Bravo AF: 0.227

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.47
PhyloP100		-0.57
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: rs437846; hg19: chr1-167863706;