rs78087585

Variant names:

• chr7-45610486-C-T
• rs78087585
• NM_021116.4:c.897C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_021116.4(ADCY1):​c.897C>T​(p.His299His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,613,608 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (28 hom.)
• Consequence: ADCY1 NM_021116.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.163
• Publications: 1 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 44

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-45610486-C-T is Benign according to our data. Variant chr7-45610486-C-T is described in ClinVar as Benign. ClinVar VariationId is 517530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.163 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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.897C>T	p.His299His	synonymous	Exon 3 of 20	NP_066939.1
	ADCY1	NM_001281768.2		c.222C>T	p.His74His	synonymous	Exon 4 of 10	NP_001268697.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.897C>T	p.His299His	synonymous	Exon 3 of 20	ENSP00000297323.7
	ADCY1	ENST00000920696.1		c.747C>T	p.His249His	synonymous	Exon 2 of 19	ENSP00000590755.1
	ADCY1	ENST00000432715.5	TSL:2	c.222C>T	p.His74His	synonymous	Exon 4 of 10	ENSP00000392721.1

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 655 AN: 152058 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00633

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00321 AC: 800 AN: 249252 AF XY: 0.00332

Gnomad AFR exome AF: 0.00621

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00387 AC: 5655 AN: 1461432 Hom.: 28 Cov.: 31 AF XY: 0.00390 AC XY: 2838 AN XY: 727042

African (AFR) AF: 0.00601 AC: 201 AN: 33472

American (AMR) AF: 0.00295 AC: 132 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 291 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00279 AC: 241 AN: 86256

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53278

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5764

European-Non Finnish (NFE) AF: 0.00386 AC: 4296 AN: 1111756

Other (OTH) AF: 0.00586 AC: 354 AN: 60372

GnomAD4 genome AF: 0.00433 AC: 659 AN: 152176 Hom.: 3 Cov.: 32 AF XY: 0.00406 AC XY: 302 AN XY: 74402

African (AFR) AF: 0.00641 AC: 266 AN: 41502

American (AMR) AF: 0.00504 AC: 77 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 33 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4820

European-Finnish (FIN) AF: 0.000849 AC: 9 AN: 10602

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00356 AC: 242 AN: 68018

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00473 Hom.: 0

Bravo AF: 0.00494

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00474

EpiControl AF: 0.00391

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.6
DANN	Benign	0.79
PhyloP100		-0.16
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs78087585; hg19: chr7-45650085;