16-90043348-GC-GCC

Variant names:

• chr16-90043348-G-GC
• rs3833069
• ENST00000517889.6:n.966dupG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000517889.6(URAHP):​n.966dupG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,602,956 control chromosomes in the GnomAD database, including 81,720 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13560 hom., cov: 0)
  • Exomes 𝑓: 0.29 (68160 hom.)
• Consequence: URAHP ENST00000517889.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.863
• Publications: 5 publications found

Genes affected

URAHP (HGNC:):

GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-90043348-G-GC is Benign according to our data. Variant chr16-90043348-G-GC is described in ClinVar as Benign. ClinVar VariationId is 402895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001481.3	c.*9dupC		3_prime_UTR_variant	Exon 11 of 11	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.*9dupC		3_prime_UTR_variant	Exon 11 of 11	1	NM_001481.3	ENSP00000268699.4

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59391 AN: 152002 Hom.: 13522 Cov.: 0

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.365 AC: 87090 AN: 238882 AF XY: 0.352

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.643

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.288 AC: 417778 AN: 1450840 Hom.: 68160 Cov.: 34 AF XY: 0.288 AC XY: 207481 AN XY: 720886

African (AFR) AF: 0.618 AC: 20572 AN: 33286

American (AMR) AF: 0.466 AC: 20606 AN: 44228

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 6143 AN: 25926

East Asian (EAS) AF: 0.677 AC: 26720 AN: 39444

South Asian (SAS) AF: 0.367 AC: 31600 AN: 86000

European-Finnish (FIN) AF: 0.409 AC: 20078 AN: 49122

Middle Eastern (MID) AF: 0.259 AC: 1434 AN: 5530

European-Non Finnish (NFE) AF: 0.246 AC: 272298 AN: 1107336

Other (OTH) AF: 0.306 AC: 18327 AN: 59968

GnomAD4 genome AF: 0.391 AC: 59480 AN: 152116 Hom.: 13560 Cov.: 0 AF XY: 0.399 AC XY: 29682 AN XY: 74358

African (AFR) AF: 0.604 AC: 25075 AN: 41502

American (AMR) AF: 0.407 AC: 6221 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3272 AN: 5140

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4828

European-Finnish (FIN) AF: 0.421 AC: 4453 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16949 AN: 67978

Other (OTH) AF: 0.330 AC: 696 AN: 2110

Alfa AF: 0.214 Hom.: 650

Bravo AF: 0.400

Asia WGS AF: 0.499 AC: 1740 AN: 3478

EpiCase AF: 0.236

EpiControl AF: 0.241

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Primary ciliary dyskinesia 33 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jan 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3833069; hg19: chr16-90109756;