rs2293106

Variant names:

• chr7-45713725-G-A
• rs2293106
• NM_021116.4:c.3090G>A
• ADCY1 p.Arg1030Arg

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021116.4(ADCY1):​c.3090G>A​(p.Arg1030Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 780,528 control chromosomes in the GnomAD database, including 11,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3429 hom., cov: 33)
  • Exomes 𝑓: 0.15 (7776 hom.)
• Consequence: ADCY1 NM_021116.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.63
• Publications: 15 publications found

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADCY1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 44

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-45713725-G-A is Benign according to our data. Variant chr7-45713725-G-A is described in ClinVar as Benign. ClinVar VariationId is 517532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	NM_021116.4	MANE Select	c.3090G>A	p.Arg1030Arg	synonymous	Exon 20 of 20	NP_066939.1	Q08828

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.3090G>A	p.Arg1030Arg	synonymous	Exon 20 of 20	ENSP00000297323.7	Q08828
	ADCY1	ENST00000920696.1		c.2940G>A	p.Arg980Arg	synonymous	Exon 19 of 19	ENSP00000590755.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29976 AN: 152158 Hom.: 3425 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.147 AC: 36842 AN: 251350 AF XY: 0.142

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.0990

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.145 AC: 91302 AN: 628252 Hom.: 7776 Cov.: 0 AF XY: 0.140 AC XY: 48050 AN XY: 342276

African (AFR) AF: 0.316 AC: 5595 AN: 17694

American (AMR) AF: 0.105 AC: 4586 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4228 AN: 20984

East Asian (EAS) AF: 0.0777 AC: 2802 AN: 36068

South Asian (SAS) AF: 0.0444 AC: 3101 AN: 69796

European-Finnish (FIN) AF: 0.129 AC: 6777 AN: 52688

Middle Eastern (MID) AF: 0.179 AC: 741 AN: 4148

European-Non Finnish (NFE) AF: 0.166 AC: 58058 AN: 350050

Other (OTH) AF: 0.164 AC: 5414 AN: 33090

GnomAD4 genome AF: 0.197 AC: 29989 AN: 152276 Hom.: 3429 Cov.: 33 AF XY: 0.192 AC XY: 14318 AN XY: 74454

African (AFR) AF: 0.315 AC: 13097 AN: 41538

American (AMR) AF: 0.140 AC: 2149 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.101 AC: 524 AN: 5170

South Asian (SAS) AF: 0.0424 AC: 205 AN: 4832

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10616

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11176 AN: 68024

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.185 Hom.: 1262

Bravo AF: 0.208

Asia WGS AF: 0.0900 AC: 319 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.183

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 44 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2293106;

hg19: chr7-45753324;

COSMIC: COSV52040452;