rs200597993

Variant names:

• chr7-45574801-C-G
• rs200597993
• NM_021116.4:c.258C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-45574801-C-G
• chr7-45574801-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_021116.4(ADCY1):​c.258C>G​(p.Pro86Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,571,524 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00069 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (10 hom.)
• Consequence: ADCY1 NM_021116.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.149
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-45574801-C-G is Benign according to our data. Variant chr7-45574801-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1317902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.149 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 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.258C>G	p.Pro86Pro	synonymous	Exon 1 of 20	NP_066939.1	Q08828
	ADCY1	NM_001281768.2		c.-330-88C>G		intron	N/A	NP_001268697.1	C9J1J0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.258C>G	p.Pro86Pro	synonymous	Exon 1 of 20	ENSP00000297323.7	Q08828
	ADCY1	ENST00000920696.1		c.258C>G	p.Pro86Pro	synonymous	Exon 1 of 19	ENSP00000590755.1
	ADCY1	ENST00000432715.5	TSL:2	c.-330-88C>G		intron	N/A	ENSP00000392721.1	C9J1J0

Frequencies

GnomAD3 genomes AF: 0.000687 AC: 104 AN: 151470 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000869

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000724

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.00152 AC: 285 AN: 187354 AF XY: 0.00181

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.000380

Gnomad ASJ exome AF: 0.00183

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000688

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.000842 AC: 1196 AN: 1419948 Hom.: 10 Cov.: 31 AF XY: 0.00106 AC XY: 747 AN XY: 705336

African (AFR) AF: 0.000306 AC: 9 AN: 29418

American (AMR) AF: 0.000425 AC: 17 AN: 39974

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 44 AN: 24832

East Asian (EAS) AF: 0.00 AC: 0 AN: 35500

South Asian (SAS) AF: 0.00675 AC: 551 AN: 81662

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48164

Middle Eastern (MID) AF: 0.0104 AC: 45 AN: 4334

European-Non Finnish (NFE) AF: 0.000415 AC: 456 AN: 1097530

Other (OTH) AF: 0.00125 AC: 73 AN: 58534

GnomAD4 genome AF: 0.000686 AC: 104 AN: 151576 Hom.: 1 Cov.: 32 AF XY: 0.000689 AC XY: 51 AN XY: 74066

African (AFR) AF: 0.000241 AC: 10 AN: 41446

American (AMR) AF: 0.00118 AC: 18 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000869 AC: 3 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000724 AC: 49 AN: 67708

Other (OTH) AF: 0.000476 AC: 1 AN: 2100

Alfa AF: 0.00110 Hom.: 2

Bravo AF: 0.000706

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.15
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism

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: rs200597993; hg19: chr7-45614400;