rs203826

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-167875315-C-A
• chr1-167875315-C-G
• chr1-167875315-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018417.6(ADCY10):​c.1407-129G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 924,788 control chromosomes in the GnomAD database, including 41,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9820 hom., cov: 32)
  • Exomes 𝑓: 0.28 (31488 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-167875315-C-A is Benign according to our data. Variant chr1-167875315-C-A is described in ClinVar as Benign. ClinVar VariationId is 1244897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51722 AN: 151966 Hom.: 9811 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.278 AC: 214558 AN: 772704 Hom.: 31488 AF XY: 0.272 AC XY: 110306 AN XY: 404822

African (AFR) AF: 0.502 AC: 9684 AN: 19286

American (AMR) AF: 0.354 AC: 12482 AN: 35290

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 6852 AN: 21028

East Asian (EAS) AF: 0.225 AC: 7532 AN: 33506

South Asian (SAS) AF: 0.181 AC: 12143 AN: 66918

European-Finnish (FIN) AF: 0.233 AC: 11475 AN: 49162

Middle Eastern (MID) AF: 0.357 AC: 1564 AN: 4384

European-Non Finnish (NFE) AF: 0.281 AC: 141957 AN: 505800

Other (OTH) AF: 0.291 AC: 10869 AN: 37330

GnomAD4 genome AF: 0.340 AC: 51774 AN: 152084 Hom.: 9820 Cov.: 32 AF XY: 0.338 AC XY: 25107 AN XY: 74362

African (AFR) AF: 0.506 AC: 20953 AN: 41444

American (AMR) AF: 0.349 AC: 5333 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5176

South Asian (SAS) AF: 0.179 AC: 862 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10582

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18808 AN: 67988

Other (OTH) AF: 0.319 AC: 674 AN: 2116

Alfa AF: 0.155 Hom.: 311

Bravo AF: 0.360

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.76
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV63243728;