rs375141353

Variant names:

• chr7-45574791-C-G
• NM_021116.4:c.248C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-45574791-C-G
• chr7-45574791-C-T

Variant summary

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

The NM_021116.4(ADCY1):​c.248C>G​(p.Ala83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,046 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADCY1 NM_021116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=0.17148185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.248C>G	p.Ala83Gly	missense_variant	Exon 1 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4	c.248C>G	p.Ala83Gly	missense_variant	Exon 1 of 19		XP_005249641.1
ADCY1	XM_005249585.3	c.248C>G	p.Ala83Gly	missense_variant	Exon 1 of 9		XP_005249642.1
ADCY1	NM_001281768.2	c.-330-98C>G		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.248C>G	p.Ala83Gly	missense_variant	Exon 1 of 20	1	NM_021116.4	ENSP00000297323.7
ADCY1	ENST00000432715.5	c.-330-98C>G		intron_variant	Intron 1 of 9	2		ENSP00000392721.1
ADCY1	ENST00000621543.1	c.-428C>G		upstream_gene_variant		5		ENSP00000479770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395046 Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2 AN XY: 691058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.15
Sift	Benign	0.37	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.56		Gain of disorder (P = 0.0737);
MVP		0.54
MPC		1.3
ClinPred		0.21	T
GERP RS		0.51
Varity_R		0.041
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: chr7-45614390;