rs1064448

Positions:

• chr16-50316972-T-G

Variant summary

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

The NM_001114.5(ADCY7):​c.*1467T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,646 control chromosomes in the GnomAD database, including 12,720 homozygotes. 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 0.38 (12656 hom., cov: 32)
  • Exomes 𝑓: 0.46 (64 hom.)
• Consequence: ADCY7 NM_001114.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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]

BRD7 (HGNC:14310): (bromodomain containing 7) This gene encodes a protein which is a member of the bromodomain-containing protein family. The product of this gene has been identified as a component of one form of the SWI/SNF chromatin remodeling complex, and as a protein which interacts with p53 and is required for p53-dependent oncogene-induced senescence which prevents tumor growth. Pseudogenes have been described on chromosomes 2, 3, 6, 13 and 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY7	NM_001114.5	c.*1467T>G		3_prime_UTR_variant	26/26	ENST00000673801.1
BRD7	NM_013263.5	c.*2239A>C		3_prime_UTR_variant	17/17	ENST00000394688.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD7	ENST00000394688.8	c.*2239A>C		3_prime_UTR_variant	17/17	1	NM_013263.5	P4
ADCY7	ENST00000673801.1	c.*1467T>G		3_prime_UTR_variant	26/26		NM_001114.5	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57543 AN: 151954 Hom.: 12657 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.458 AC: 263 AN: 574 Hom.: 64 Cov.: 0 AF XY: 0.455 AC XY: 153 AN XY: 336

Gnomad4 EAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.379 AC: 57570 AN: 152072 Hom.: 12656 Cov.: 32 AF XY: 0.376 AC XY: 27915 AN XY: 74334

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.419

Alfa AF: 0.465 Hom.: 13225

Bravo AF: 0.368

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs1064448; hg19: chr16-50350883;