1-167875315-C-G

Variant names:

• chr1-167875315-C-G
• rs203826
• NM_018417.6:c.1407-129G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018417.6(ADCY10):​c.1407-129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.1407-129G>C		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.1131-129G>C		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.948-129G>C		intron	N/A	NP_001161221.1	Q96PN6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.1407-129G>C		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.1131-129G>C		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000545172.5	TSL:2	c.948-129G>C		intron	N/A	ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000388 AC: 3 AN: 774104 Hom.: 0 AF XY: 0.00000493 AC XY: 2 AN XY: 405498

African (AFR) AF: 0.000155 AC: 3 AN: 19324

American (AMR) AF: 0.00 AC: 0 AN: 35320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21056

East Asian (EAS) AF: 0.00 AC: 0 AN: 33546

South Asian (SAS) AF: 0.00 AC: 0 AN: 66950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506938

Other (OTH) AF: 0.00 AC: 0 AN: 37376

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74262

African (AFR) AF: 0.0000726 AC: 3 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.78
DANN	Benign	0.25
PhyloP100		-0.091

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs203826; hg19: chr1-167844553;