1-167875315-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_018417.6(ADCY10):​c.1407-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 774,104 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: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAdExome4 at 13 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.1407-129G>A		intron_variant	Intron 12 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.1407-129G>A		intron_variant	Intron 12 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.1131-129G>A		intron_variant	Intron 12 of 32	1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.948-129G>A		intron_variant	Intron 9 of 29	2		ENSP00000441992.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000168 AC: 13 AN: 774104 Hom.: 0 AF XY: 0.0000123 AC XY: 5 AN XY: 405498

African (AFR) AF: 0.00 AC: 0 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: 0.0000149 AC: 1 AN: 66950

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

Middle Eastern (MID) AF: 0.000683 AC: 3 AN: 4390

European-Non Finnish (NFE) AF: 0.0000178 AC: 9 AN: 506938

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.94
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;