16-50311867-T-C

Position:

• chr16-50311867-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114.5(ADCY7):​c.2448+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.69 (29295 hom., cov: 20)
  • Exomes 𝑓: 0.67 (250522 hom.)
• Consequence: ADCY7 NM_001114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

Genes affected

ADCY7 (HGNC:238): (adenylate cyclase 7) This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.2448+81T>C		intron_variant		ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.2448+81T>C		intron_variant			NM_001114.5	ENSP00000501053	P1
ADCY7	ENST00000254235.7	c.2448+81T>C		intron_variant		1		ENSP00000254235	P1
ADCY7	ENST00000394697.7	c.2448+81T>C		intron_variant		5		ENSP00000378187	P1
ADCY7	ENST00000673973.1	c.*820+81T>C		intron_variant, NMD_transcript_variant				ENSP00000501223

Frequencies

GnomAD3 genomes AF: 0.686 AC: 90889 AN: 132430 Hom.: 29252 Cov.: 20

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.711

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.700

GnomAD4 exome AF: 0.672 AC: 772676 AN: 1149810 Hom.: 250522 Cov.: 17 AF XY: 0.671 AC XY: 390757 AN XY: 582444

Gnomad4 AFR exome AF: 0.657

Gnomad4 AMR exome AF: 0.809

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.686 AC: 91004 AN: 132580 Hom.: 29295 Cov.: 20 AF XY: 0.685 AC XY: 43616 AN XY: 63644

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.702

Alfa AF: 0.635 Hom.: 25913

Bravo AF: 0.646

Asia WGS AF: 0.570 AC: 1987 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.053
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2302679; hg19: chr16-50345778; COSMIC: COSV54270161; COSMIC: COSV54270161;