chr16-90022905-C-T

Variant names:

• chr16-90022905-C-T
• rs58490907
• NM_001481.3:c.3+181C>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+181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,224 control chromosomes in the GnomAD database, including 1,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.068 (1055 hom., cov: 33)
• Consequence: DRC4 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, G2P, 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=-0.91).
• BP6: Variant 16-90022905-C-T is Benign according to our data. Variant chr16-90022905-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 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+181C>T		intron	N/A	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.-73+3137C>T		intron	N/A	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.-370+181C>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+181C>T		intron	N/A	ENSP00000268699.4	O95995-1
	GAS8	ENST00000564853.1	TSL:1	n.55+181C>T		intron	N/A
	GAS8	ENST00000566266.5	TSL:1	n.3+181C>T		intron	N/A	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10304 AN: 152106 Hom.: 1057 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0678 AC: 10317 AN: 152224 Hom.: 1055 Cov.: 33 AF XY: 0.0651 AC XY: 4846 AN XY: 74430

African (AFR) AF: 0.219 AC: 9099 AN: 41522

American (AMR) AF: 0.0312 AC: 477 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4826

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00559 AC: 380 AN: 68000

Other (OTH) AF: 0.0493 AC: 104 AN: 2110

Alfa AF: 0.00360 Hom.: 1

Bravo AF: 0.0749

Asia WGS AF: 0.0280 AC: 97 AN: 3476

ClinVar

ClinVar submissions as Germline

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	-0.91
CADD	Benign	2.4
DANN	Benign	0.86
PhyloP100		-1.4
PromoterAI		-0.021	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: rs58490907; hg19: chr16-90089313;