rs203849

Variant names:

• chr1-167880176-A-G
• rs203849
• NM_018417.6:c.1155T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018417.6(ADCY10):​c.1155T>C​(p.Gly385Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,610,082 control chromosomes in the GnomAD database, including 187,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20842 hom., cov: 32)
  • Exomes 𝑓: 0.48 (166937 hom.)
• Consequence: ADCY10 NM_018417.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.909
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-167880176-A-G is Benign according to our data. Variant chr1-167880176-A-G is described in ClinVar as Benign. ClinVar VariationId is 1167837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.909 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.1155T>C	p.Gly385Gly	synonymous	Exon 11 of 33	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.879T>C	p.Gly293Gly	synonymous	Exon 11 of 33	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.696T>C	p.Gly232Gly	synonymous	Exon 8 of 30	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.1155T>C	p.Gly385Gly	synonymous	Exon 11 of 33	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.879T>C	p.Gly293Gly	synonymous	Exon 11 of 33	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000545172.5	TSL:2	c.696T>C	p.Gly232Gly	synonymous	Exon 8 of 30	ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78436 AN: 151936 Hom.: 20819 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.473 AC: 117391 AN: 247990 AF XY: 0.472

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.478

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.325

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.476 AC: 694420 AN: 1458028 Hom.: 166937 Cov.: 38 AF XY: 0.476 AC XY: 345478 AN XY: 725160

African (AFR) AF: 0.635 AC: 21232 AN: 33432

American (AMR) AF: 0.478 AC: 21207 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 13683 AN: 26094

East Asian (EAS) AF: 0.359 AC: 14246 AN: 39658

South Asian (SAS) AF: 0.462 AC: 39608 AN: 85676

European-Finnish (FIN) AF: 0.454 AC: 24190 AN: 53296

Middle Eastern (MID) AF: 0.581 AC: 3327 AN: 5724

European-Non Finnish (NFE) AF: 0.476 AC: 527994 AN: 1109536

Other (OTH) AF: 0.480 AC: 28933 AN: 60254

GnomAD4 genome AF: 0.516 AC: 78507 AN: 152054 Hom.: 20842 Cov.: 32 AF XY: 0.514 AC XY: 38213 AN XY: 74342

African (AFR) AF: 0.637 AC: 26423 AN: 41468

American (AMR) AF: 0.489 AC: 7478 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1734 AN: 5168

South Asian (SAS) AF: 0.463 AC: 2230 AN: 4816

European-Finnish (FIN) AF: 0.451 AC: 4765 AN: 10562

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32368 AN: 67978

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.489 Hom.: 78715

Bravo AF: 0.522

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs203849; hg19: chr1-167849414; COSMIC: COSV63239261;