16-90040291-T-C

Variant names:

• chr16-90040291-T-C
• rs1555651546
• ENST00000409873.5:n.819A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000409873.5(URAHP):​n.819A>G 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 0.000000705 in 1,417,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: URAHP ENST00000409873.5 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.384
• Publications: 0 publications found

Genes affected

URAHP (HGNC:):

DRC4 (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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-90040291-T-C is Benign according to our data. Variant chr16-90040291-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 542267.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409873.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC4	NM_001481.3	MANE Select	c.1012-9T>C		intron	N/A	NP_001472.1
	URAHP	NR_027335.2		n.819A>G		non_coding_transcript_exon	Exon 5 of 5
	DRC4	NM_001286209.2		c.937-9T>C		intron	N/A	NP_001273138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URAHP	ENST00000409873.5	TSL:1	n.819A>G		non_coding_transcript_exon	Exon 5 of 5
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1012-9T>C		intron	N/A	ENSP00000268699.4
	GAS8	ENST00000566266.5	TSL:1	n.*972-9T>C		intron	N/A	ENSP00000454343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417480 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 701200

African (AFR) AF: 0.00 AC: 0 AN: 32328

American (AMR) AF: 0.00 AC: 0 AN: 38230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 36990

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089968

Other (OTH) AF: 0.00 AC: 0 AN: 58724

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:1

Mar 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1555651546; hg19: chr16-90106699;