16-90031453-G-T

Variant names:

• chr16-90031453-G-T
• rs884928
• NM_001481.3:c.245G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001286205.2(DRC4):​c.-5G>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000106 in 1,600,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DRC4 NM_001286205.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.62
• Publications: 4 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]

DRC4 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 33

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3297668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286205.2. 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.245G>T	p.Arg82Leu	missense	Exon 3 of 11	NP_001472.1	O95995-1
	DRC4	NM_001286205.2		c.-5G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001273134.1
	DRC4	NM_001286208.2		c.-277G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001273137.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.245G>T	p.Arg82Leu	missense	Exon 3 of 11	ENSP00000268699.4	O95995-1
	GAS8	ENST00000566266.5	TSL:1	n.*260G>T		non_coding_transcript_exon	Exon 3 of 10	ENSP00000454343.1	H3BME0
	GAS8	ENST00000566266.5	TSL:1	n.*260G>T		3_prime_UTR	Exon 3 of 10	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000228 AC: 5 AN: 219044 AF XY: 0.0000337

Gnomad AFR exome AF: 0.000148

Gnomad AMR exome AF: 0.0000657

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000641

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000552 AC: 8 AN: 1448220 Hom.: 0 Cov.: 32 AF XY: 0.00000834 AC XY: 6 AN XY: 719288

African (AFR) AF: 0.000150 AC: 5 AN: 33242

American (AMR) AF: 0.0000479 AC: 2 AN: 41758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38860

South Asian (SAS) AF: 0.00 AC: 0 AN: 84474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105952

Other (OTH) AF: 0.00 AC: 0 AN: 59942

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74504

African (AFR) AF: 0.000217 AC: 9 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.0000264

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.17	T
PhyloP100		6.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.19		Loss of MoRF binding (P = 0.0579)
MVP		0.59
MPC		0.15
ClinPred		0.87	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.46
Mutation Taster		=44/56	disease causing

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: rs884928; hg19: chr16-90097861;