7-45692001-C-G

Variant names:

• chr7-45692001-C-G
• rs11766222
• NM_021116.4:c.2454+5328C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021116.4(ADCY1):​c.2454+5328C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADCY1 NM_021116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.2454+5328C>G		intron_variant	Intron 14 of 19	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4	c.2454+5328C>G		intron_variant	Intron 14 of 18		XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12	c.2454+5328C>G		intron_variant	Intron 14 of 19	1	NM_021116.4	ENSP00000297323.7

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.34

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: rs11766222; hg19: chr7-45731600;