chr1-167894468-G-A

Position:

• chr1-167894468-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.740-527C>T		intron_variant		ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.740-527C>T		intron_variant		1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.464-527C>T		intron_variant		1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.281-527C>T		intron_variant		2		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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.224

Alfa AF: 0.217 Hom.: 7494

Bravo AF: 0.227

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.47

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: rs437846; hg19: chr1-167863706;