16-90044871-G-T

Variant names:

• chr16-90044871-G-T
• rs8577
• NM_001481.3:c.*1526G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001481.3(DRC4):​c.*1526G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 234,702 control chromosomes in the GnomAD database, including 16,302 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 0.37 (12194 hom., cov: 33)
  • Exomes 𝑓: 0.29 (4108 hom.)
• Consequence: DRC4 NM_001481.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 9 publications found

Genes affected

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:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC4	NM_001481.3	MANE Select	c.*1526G>T		3_prime_UTR	Exon 11 of 11	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.*1526G>T		3_prime_UTR	Exon 11 of 11	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.*1526G>T		3_prime_UTR	Exon 11 of 11	NP_001273134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.*1526G>T		3_prime_UTR	Exon 11 of 11	ENSP00000268699.4	O95995-1
	GAS8	ENST00000566266.5	TSL:1	n.*2923G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000454343.1	H3BME0
	GAS8	ENST00000566266.5	TSL:1	n.*2923G>T		3_prime_UTR	Exon 10 of 10	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56902 AN: 151948 Hom.: 12159 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.288 AC: 23795 AN: 82636 Hom.: 4108 Cov.: 0 AF XY: 0.290 AC XY: 12853 AN XY: 44266

African (AFR) AF: 0.525 AC: 915 AN: 1742

American (AMR) AF: 0.414 AC: 1675 AN: 4044

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 371 AN: 1792

East Asian (EAS) AF: 0.648 AC: 1923 AN: 2968

South Asian (SAS) AF: 0.314 AC: 4797 AN: 15270

European-Finnish (FIN) AF: 0.385 AC: 1493 AN: 3882

Middle Eastern (MID) AF: 0.259 AC: 90 AN: 348

European-Non Finnish (NFE) AF: 0.233 AC: 11251 AN: 48278

Other (OTH) AF: 0.297 AC: 1280 AN: 4312

GnomAD4 genome AF: 0.375 AC: 56996 AN: 152066 Hom.: 12194 Cov.: 33 AF XY: 0.383 AC XY: 28430 AN XY: 74322

African (AFR) AF: 0.555 AC: 23009 AN: 41450

American (AMR) AF: 0.397 AC: 6075 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3464

East Asian (EAS) AF: 0.632 AC: 3268 AN: 5168

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4447 AN: 10572

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16804 AN: 67980

Other (OTH) AF: 0.320 AC: 677 AN: 2116

Alfa AF: 0.293 Hom.: 1498

Bravo AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.086
DANN	Benign	0.58
PhyloP100		-1.3
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: rs8577; hg19: chr16-90111279;