rs870856

Variant names:

• chr16-90023055-C-G
• rs870856
• NM_001481.3:c.3+331C>G

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+331C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,052 control chromosomes in the GnomAD database, including 7,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.32 (7805 hom., cov: 32)
• Consequence: DRC4 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.02
• Publications: 10 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=-0.92).
• BP6: Variant 16-90023055-C-G is Benign according to our data. Variant chr16-90023055-C-G is described in ClinVar as Benign. ClinVar VariationId is 1222931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 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+331C>G		intron	N/A	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.-73+3287C>G		intron	N/A	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.-370+331C>G		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+331C>G		intron	N/A	ENSP00000268699.4	O95995-1
	GAS8	ENST00000564853.1	TSL:1	n.55+331C>G		intron	N/A
	GAS8	ENST00000566266.5	TSL:1	n.3+331C>G		intron	N/A	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48209 AN: 151932 Hom.: 7791 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.317 AC: 48254 AN: 152052 Hom.: 7805 Cov.: 32 AF XY: 0.317 AC XY: 23559 AN XY: 74328

African (AFR) AF: 0.327 AC: 13566 AN: 41486

American (AMR) AF: 0.332 AC: 5074 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1013 AN: 5144

South Asian (SAS) AF: 0.420 AC: 2019 AN: 4810

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10586

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21696 AN: 67942

Other (OTH) AF: 0.341 AC: 721 AN: 2114

Alfa AF: 0.316 Hom.: 951

Bravo AF: 0.315

Asia WGS AF: 0.315 AC: 1094 AN: 3478

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	-0.92
CADD	Benign	0.70
DANN	Benign	0.79
PhyloP100		-2.0
PromoterAI		0.058	Neutral
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: rs870856; hg19: chr16-90089463;