7-45574628-C-A

Variant names:

• chr7-45574628-C-A
• NM_021116.4:c.85C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021116.4(ADCY1):​c.85C>A​(p.Arg29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: ADCY1 NM_021116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12572008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 19		XP_005249641.1
ADCY1	XM_005249585.3	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 9		XP_005249642.1
ADCY1	NM_001281768.2	c.-330-261C>A		intron_variant	Intron 1 of 9		NP_001268697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 20	1	NM_021116.4	ENSP00000297323.7
ADCY1	ENST00000432715.5	c.-330-261C>A		intron_variant	Intron 1 of 9	2		ENSP00000392721.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049780 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 496564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000440

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.20
Sift	Benign	0.63	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.24		Gain of glycosylation at R29 (P = 0.0041);
MVP		0.46
MPC		1.4
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.14
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-45614227;