7-45664372-G-T

Variant names:

• chr7-45664372-G-T
• rs1042009
• NM_021116.4:c.1605+2158G>T

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.1605+2158G>T 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: 31)
• Consequence: ADCY1 NM_021116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• 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: 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=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.1605+2158G>T		intron_variant	Intron 8 of 19	ENST00000297323.12	NP_066939.1
ADCY1	NM_001281768.2	c.1014G>T	p.Thr338Thr	synonymous_variant	Exon 10 of 10		NP_001268697.1
ADCY1	XM_005249585.3	c.1689G>T	p.Thr563Thr	synonymous_variant	Exon 9 of 9		XP_005249642.1
ADCY1	XM_005249584.4	c.1605+2158G>T		intron_variant	Intron 8 of 18		XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12	c.1605+2158G>T		intron_variant	Intron 8 of 19	1	NM_021116.4	ENSP00000297323.7
ADCY1	ENST00000432715.5	c.1014G>T	p.Thr338Thr	synonymous_variant	Exon 10 of 10	2		ENSP00000392721.1
ADCY1	ENST00000621543.1	c.1014G>T	p.Thr338Thr	synonymous_variant	Exon 9 of 9	5		ENSP00000479770.1
ADCY1	ENST00000646653.1	n.546+2158G>T		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.38
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: rs1042009; hg19: chr7-45703971;