chr1-167877390-A-G

Position:

• chr1-167877390-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018417.6(ADCY10):​c.1406+1056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,216 control chromosomes in the GnomAD database, including 10,735 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 0.36 (10735 hom., cov: 29)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.1406+1056T>C		intron_variant		ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.1406+1056T>C		intron_variant		1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.1130+1056T>C		intron_variant		1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.947+1056T>C		intron_variant		2		ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54580 AN: 151098 Hom.: 10718 Cov.: 29

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.361 AC: 54647 AN: 151216 Hom.: 10735 Cov.: 29 AF XY: 0.359 AC XY: 26569 AN XY: 73908

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.335

Alfa AF: 0.324 Hom.: 1430

Bravo AF: 0.379

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.8
DANN	Benign	0.73

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: rs203835; hg19: chr1-167846628;