1-167856368-A-G

Variant names:

• chr1-167856368-A-G
• rs2071922
• NM_018417.6:c.1968T>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.1968T>C​(p.Phe656Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,870 control chromosomes in the GnomAD database, including 18,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1955 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16693 hom.)
• Consequence: ADCY10 NM_018417.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00700
• Publications: 12 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]

ADCY10 Gene-Disease associations (from GenCC):

• hypercalciuria, absorptive, 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• idiopathic inherited hypercalciuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-167856368-A-G is Benign according to our data. Variant chr1-167856368-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.007 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.1968T>C	p.Phe656Phe	synonymous_variant	Exon 17 of 33	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.1968T>C	p.Phe656Phe	synonymous_variant	Exon 17 of 33	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.1692T>C	p.Phe564Phe	synonymous_variant	Exon 17 of 33	1		ENSP00000356822.1
ADCY10	ENST00000545172.5	c.1509T>C	p.Phe503Phe	synonymous_variant	Exon 14 of 30	2		ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21977 AN: 151988 Hom.: 1944 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.188 AC: 47201 AN: 251390 AF XY: 0.181

Gnomad AFR exome AF: 0.0946

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.135 AC: 197580 AN: 1461764 Hom.: 16693 Cov.: 37 AF XY: 0.137 AC XY: 99276 AN XY: 727176

African (AFR) AF: 0.0983 AC: 3290 AN: 33480

American (AMR) AF: 0.321 AC: 14369 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3930 AN: 26132

East Asian (EAS) AF: 0.416 AC: 16526 AN: 39700

South Asian (SAS) AF: 0.191 AC: 16444 AN: 86254

European-Finnish (FIN) AF: 0.199 AC: 10617 AN: 53420

Middle Eastern (MID) AF: 0.221 AC: 1272 AN: 5768

European-Non Finnish (NFE) AF: 0.110 AC: 122301 AN: 1111896

Other (OTH) AF: 0.146 AC: 8831 AN: 60390

GnomAD4 genome AF: 0.145 AC: 22010 AN: 152106 Hom.: 1955 Cov.: 32 AF XY: 0.154 AC XY: 11421 AN XY: 74344

African (AFR) AF: 0.0974 AC: 4043 AN: 41514

American (AMR) AF: 0.242 AC: 3702 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5156

South Asian (SAS) AF: 0.207 AC: 996 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2205 AN: 10562

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7732 AN: 67986

Other (OTH) AF: 0.186 AC: 392 AN: 2110

Alfa AF: 0.132 Hom.: 5482

Bravo AF: 0.150

Asia WGS AF: 0.312 AC: 1085 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.123

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.95
CADD	Benign	4.6
DANN	Benign	0.34
PhyloP100		0.0070
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: rs2071922; hg19: chr1-167825606; COSMIC: COSV63239197;