chr16-90043303-A-G

Variant names:

• chr16-90043303-A-G
• rs3743825
• NM_001481.3:c.1395A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001481.3(DRC4):​c.1395A>G​(p.Thr465Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,612,574 control chromosomes in the GnomAD database, including 496,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T465T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.82 (52147 hom., cov: 33)
  • Exomes 𝑓: 0.78 (444443 hom.)
• Consequence: DRC4 NM_001481.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.69
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-90043303-A-G is Benign according to our data. Variant chr16-90043303-A-G is described in ClinVar as Benign. ClinVar VariationId is 402894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC4	NM_001481.3	MANE Select	c.1395A>G	p.Thr465Thr	synonymous	Exon 11 of 11	NP_001472.1
	DRC4	NM_001286209.2		c.1320A>G	p.Thr440Thr	synonymous	Exon 11 of 11	NP_001273138.1
	DRC4	NM_001286205.2		c.1146A>G	p.Thr382Thr	synonymous	Exon 11 of 11	NP_001273134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1395A>G	p.Thr465Thr	synonymous	Exon 11 of 11	ENSP00000268699.4
	URAHP	ENST00000517889.6	TSL:1	n.1012T>C		non_coding_transcript_exon	Exon 4 of 4
	GAS8	ENST00000566266.5	TSL:1	n.*1355A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000454343.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125028 AN: 152026 Hom.: 52085 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.795 AC: 196742 AN: 247578 AF XY: 0.786

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.832

Gnomad EAS exome AF: 0.818

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.779 AC: 1137357 AN: 1460430 Hom.: 444443 Cov.: 57 AF XY: 0.777 AC XY: 564604 AN XY: 726514

African (AFR) AF: 0.961 AC: 32171 AN: 33474

American (AMR) AF: 0.837 AC: 37394 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 21868 AN: 26124

East Asian (EAS) AF: 0.828 AC: 32868 AN: 39692

South Asian (SAS) AF: 0.774 AC: 66707 AN: 86238

European-Finnish (FIN) AF: 0.820 AC: 42961 AN: 52388

Middle Eastern (MID) AF: 0.711 AC: 4094 AN: 5758

European-Non Finnish (NFE) AF: 0.766 AC: 852015 AN: 1111700

Other (OTH) AF: 0.783 AC: 47279 AN: 60366

GnomAD4 genome AF: 0.823 AC: 125147 AN: 152144 Hom.: 52147 Cov.: 33 AF XY: 0.823 AC XY: 61195 AN XY: 74358

African (AFR) AF: 0.956 AC: 39713 AN: 41560

American (AMR) AF: 0.786 AC: 12034 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2917 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4208 AN: 5114

South Asian (SAS) AF: 0.784 AC: 3777 AN: 4816

European-Finnish (FIN) AF: 0.821 AC: 8710 AN: 10608

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51319 AN: 67954

Other (OTH) AF: 0.769 AC: 1628 AN: 2116

Alfa AF: 0.776 Hom.: 24716

Bravo AF: 0.829

Asia WGS AF: 0.804 AC: 2800 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.031
DANN	Benign	0.34
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3743825; hg19: chr16-90109711; COSMIC: COSV108045681; COSMIC: COSV108045681;