rs61734731

Variant names:

• chr16-90040338-C-T
• rs61734731
• NM_001481.3:c.1050C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-90040338-C-T
• chr16-90040338-C-A
• chr16-90040338-C-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.1050C>T​(p.Thr350Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,601,376 control chromosomes in the GnomAD database, including 2,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (145 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2541 hom.)
• Consequence: DRC4 NM_001481.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.60
• Publications: 6 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=-0.93).
• BP6: Variant 16-90040338-C-T is Benign according to our data. Variant chr16-90040338-C-T is described in ClinVar as Benign. ClinVar VariationId is 402893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 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.1050C>T	p.Thr350Thr	synonymous	Exon 9 of 11	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.975C>T	p.Thr325Thr	synonymous	Exon 9 of 11	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.801C>T	p.Thr267Thr	synonymous	Exon 9 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.1050C>T	p.Thr350Thr	synonymous	Exon 9 of 11	ENSP00000268699.4	O95995-1
	URAHP	ENST00000409873.5	TSL:1	n.772G>A		non_coding_transcript_exon	Exon 5 of 5
	GAS8	ENST00000566266.5	TSL:1	n.*1010C>T		non_coding_transcript_exon	Exon 8 of 10	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6220 AN: 152184 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0395 AC: 9004 AN: 228100 AF XY: 0.0397

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0474

Gnomad EAS exome AF: 0.0337

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0549 AC: 79604 AN: 1449074 Hom.: 2541 Cov.: 32 AF XY: 0.0539 AC XY: 38772 AN XY: 719546

African (AFR) AF: 0.0105 AC: 348 AN: 33220

American (AMR) AF: 0.0131 AC: 565 AN: 43138

Ashkenazi Jewish (ASJ) AF: 0.0471 AC: 1218 AN: 25852

East Asian (EAS) AF: 0.0217 AC: 843 AN: 38930

South Asian (SAS) AF: 0.0175 AC: 1469 AN: 84064

European-Finnish (FIN) AF: 0.0601 AC: 3140 AN: 52246

Middle Eastern (MID) AF: 0.00994 AC: 56 AN: 5632

European-Non Finnish (NFE) AF: 0.0623 AC: 68925 AN: 1106152

Other (OTH) AF: 0.0508 AC: 3040 AN: 59840

GnomAD4 genome AF: 0.0408 AC: 6217 AN: 152302 Hom.: 145 Cov.: 32 AF XY: 0.0399 AC XY: 2968 AN XY: 74476

African (AFR) AF: 0.0133 AC: 552 AN: 41584

American (AMR) AF: 0.0187 AC: 286 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3470

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5190

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4826

European-Finnish (FIN) AF: 0.0582 AC: 618 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0614 AC: 4179 AN: 68008

Other (OTH) AF: 0.0275 AC: 58 AN: 2106

Alfa AF: 0.0465 Hom.: 134

Bravo AF: 0.0360

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 33 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.74
PhyloP100		-5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs61734731; hg19: chr16-90106746;