rs552480254

Variant names:

• chr16-90022730-C-G
• rs552480254
• NM_001481.3:c.3+6C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-90022730-C-G
• chr16-90022730-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001481.3(DRC4):​c.3+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,263,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: DRC4 NM_001481.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001237
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• 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), Ambry Genetics, G2P, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001481.3	c.3+6C>G		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.3+6C>G		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_001481.3	ENSP00000268699.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000153 AC: 1 AN: 65314 AF XY: 0.0000266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1263380 Hom.: 0 Cov.: 31 AF XY: 0.00000324 AC XY: 2 AN XY: 616480

African (AFR) AF: 0.00 AC: 0 AN: 26052

American (AMR) AF: 0.00 AC: 0 AN: 24074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21320

East Asian (EAS) AF: 0.00 AC: 0 AN: 28588

South Asian (SAS) AF: 0.0000298 AC: 2 AN: 67106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1009988

Other (OTH) AF: 0.00 AC: 0 AN: 51660

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.9
DANN	Benign	0.83
PhyloP100		-0.45
PromoterAI		-0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.010
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: rs552480254; hg19: chr16-90089138;