16-90022899-C-T

Variant names:

• chr16-90022899-C-T
• rs112094183
• NM_001481.3:c.3+175C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001481.3(DRC4):​c.3+175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,166 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.040 (320 hom., cov: 33)
• Consequence: DRC4 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13
• Publications: 0 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-90022899-C-T is Benign according to our data. Variant chr16-90022899-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 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.3+175C>T		intron	N/A	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.-73+3131C>T		intron	N/A	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.-370+175C>T		intron	N/A	NP_001273134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.3+175C>T		intron	N/A	ENSP00000268699.4	O95995-1
	GAS8	ENST00000564853.1	TSL:1	n.55+175C>T		intron	N/A
	GAS8	ENST00000566266.5	TSL:1	n.3+175C>T		intron	N/A	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6123 AN: 152048 Hom.: 316 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0404 AC: 6150 AN: 152166 Hom.: 320 Cov.: 33 AF XY: 0.0391 AC XY: 2907 AN XY: 74402

African (AFR) AF: 0.116 AC: 4803 AN: 41500

American (AMR) AF: 0.0296 AC: 453 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4826

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 745 AN: 67982

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0245 Hom.: 13

Bravo AF: 0.0440

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.90
PhyloP100		-1.1
PromoterAI		-0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs112094183; hg19: chr16-90089307;