rs1872691

Positions:

• chr16-50316299-G-A
• chr16-50316299-G-C

Variant summary

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

The NM_001114.5(ADCY7):​c.*794G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,290 control chromosomes in the GnomAD database, including 6,407 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 0.27 (6405 hom., cov: 33)
  • Exomes 𝑓: 0.18 (2 hom.)
• Consequence: ADCY7 NM_001114.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY7	NM_001114.5	c.*794G>A		3_prime_UTR_variant	26/26	ENST00000673801.1	NP_001105.1
BRD7	NM_013263.5	c.*2912C>T		3_prime_UTR_variant	17/17	ENST00000394688.8	NP_037395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY7	ENST00000673801.1	c.*794G>A		3_prime_UTR_variant	26/26		NM_001114.5	ENSP00000501053.1
BRD7	ENST00000394688	c.*2912C>T		3_prime_UTR_variant	17/17	1	NM_013263.5	ENSP00000378180.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40942 AN: 151974 Hom.: 6393 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.182 AC: 36 AN: 198 Hom.: 2 Cov.: 0 AF XY: 0.153 AC XY: 18 AN XY: 118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.270 AC: 40999 AN: 152092 Hom.: 6405 Cov.: 33 AF XY: 0.270 AC XY: 20058 AN XY: 74348

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.241

Alfa AF: 0.203 Hom.: 3413

Bravo AF: 0.287

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1872691; hg19: chr16-50350210;