chr16-90037837-C-A

Variant names:

• chr16-90037837-C-A
• rs755553133
• NM_001481.3:c.1000C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001481.3(DRC4):​c.1000C>A​(p.Arg334Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R334R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRC4 NM_001481.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.324
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 16-90037837-C-A is Benign according to our data. Variant chr16-90037837-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2023750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.324 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC4	NM_001481.3	MANE Select	c.1000C>A	p.Arg334Arg	synonymous	Exon 8 of 11	NP_001472.1
	DRC4	NM_001286209.2		c.925C>A	p.Arg309Arg	synonymous	Exon 8 of 11	NP_001273138.1
	DRC4	NM_001286205.2		c.751C>A	p.Arg251Arg	synonymous	Exon 8 of 11	NP_001273134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1000C>A	p.Arg334Arg	synonymous	Exon 8 of 11	ENSP00000268699.4
	GAS8	ENST00000566266.5	TSL:1	n.*960C>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000454343.1
	GAS8	ENST00000566266.5	TSL:1	n.*960C>A		3_prime_UTR	Exon 7 of 10	ENSP00000454343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 33 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs755553133; hg19: chr16-90104245;