rs203818

Variant names:

• chr1-167868736-A-G
• rs203818
• NM_018417.6:c.1616+1521T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-167868736-A-G
• chr1-167868736-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018417.6(ADCY10):​c.1616+1521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,140 control chromosomes in the GnomAD database, including 17,695 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 0.43 (17695 hom., cov: 32)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.1616+1521T>C		intron_variant	Intron 14 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.1616+1521T>C		intron_variant	Intron 14 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.1340+1521T>C		intron_variant	Intron 14 of 32	1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.1157+1521T>C		intron_variant	Intron 11 of 29	2		ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65609 AN: 152020 Hom.: 17663 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.432 AC: 65695 AN: 152140 Hom.: 17695 Cov.: 32 AF XY: 0.433 AC XY: 32209 AN XY: 74384

African (AFR) AF: 0.761 AC: 31575 AN: 41498

American (AMR) AF: 0.295 AC: 4516 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2827 AN: 5174

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3886 AN: 10576

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18790 AN: 67992

Other (OTH) AF: 0.389 AC: 821 AN: 2112

Alfa AF: 0.356 Hom.: 1924

Bravo AF: 0.442

Asia WGS AF: 0.478 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.25
DANN	Benign	0.60
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs203818; hg19: chr1-167837974;