rs203818

Positions:

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

Variant summary

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

The ENST00000367851.9(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 ENST00000367851.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.1616+1521T>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.1616+1521T>C		intron_variant		1	NM_018417.6	ENSP00000356825	P1
ADCY10	ENST00000367848.1	c.1340+1521T>C		intron_variant		1		ENSP00000356822
ADCY10	ENST00000545172.5	c.1157+1521T>C		intron_variant		2		ENSP00000441992

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

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.389

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

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: rs203818; hg19: chr1-167837974;