1-167855896-A-G

Variant names:

• chr1-167855896-A-G
• rs7512378
• NM_018417.6:c.2171+269T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018417.6(ADCY10):​c.2171+269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,968 control chromosomes in the GnomAD database, including 5,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5636 hom., cov: 32)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 1-167855896-A-G is Benign according to our data. Variant chr1-167855896-A-G is described in ClinVar as [Benign]. Clinvar id is 1269849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.2171+269T>C		intron_variant	Intron 17 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.2171+269T>C		intron_variant	Intron 17 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.1895+269T>C		intron_variant	Intron 17 of 32	1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.1712+269T>C		intron_variant	Intron 14 of 29	2		ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41134 AN: 151850 Hom.: 5628 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.271 AC: 41161 AN: 151968 Hom.: 5636 Cov.: 32 AF XY: 0.266 AC XY: 19756 AN XY: 74256

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.240

Alfa AF: 0.268 Hom.: 8655

Bravo AF: 0.271

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.22
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs7512378; hg19: chr1-167825134;