NM_001114.5:c.2448+81T>C

Variant names:

• chr16-50311867-T-C
• rs2302679
• NM_001114.5:c.2448+81T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.2448+81T>C		intron_variant	Intron 20 of 25	ENST00000673801.1	NP_001105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.2448+81T>C		intron_variant	Intron 20 of 25		NM_001114.5	ENSP00000501053.1
ADCY7	ENST00000254235.7	c.2448+81T>C		intron_variant	Intron 19 of 24	1		ENSP00000254235.3
ADCY7	ENST00000394697.7	c.2448+81T>C		intron_variant	Intron 20 of 25	5		ENSP00000378187.2
ADCY7	ENST00000673973.1	n.*820+81T>C		intron_variant	Intron 20 of 25			ENSP00000501223.1

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

African (AFR) AF: 0.657 AC: 17618 AN: 26824

American (AMR) AF: 0.809 AC: 34842 AN: 43088

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 16289 AN: 22998

East Asian (EAS) AF: 0.571 AC: 16935 AN: 29666

South Asian (SAS) AF: 0.676 AC: 52376 AN: 77504

European-Finnish (FIN) AF: 0.580 AC: 26410 AN: 45520

Middle Eastern (MID) AF: 0.682 AC: 2742 AN: 4020

European-Non Finnish (NFE) AF: 0.673 AC: 572624 AN: 851478

Other (OTH) AF: 0.674 AC: 32840 AN: 48712

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

African (AFR) AF: 0.687 AC: 24146 AN: 35152

American (AMR) AF: 0.785 AC: 10607 AN: 13508

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2335 AN: 3304

East Asian (EAS) AF: 0.528 AC: 1880 AN: 3562

South Asian (SAS) AF: 0.700 AC: 2922 AN: 4172

European-Finnish (FIN) AF: 0.615 AC: 4229 AN: 6882

Middle Eastern (MID) AF: 0.708 AC: 170 AN: 240

European-Non Finnish (NFE) AF: 0.678 AC: 42739 AN: 63050

Other (OTH) AF: 0.702 AC: 1299 AN: 1850

Alfa AF: 0.640 Hom.: 35501

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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