NM_001481.3:c.3+203C>T

Variant names:

• chr16-90022927-C-T
• rs59443037
• NM_001481.3:c.3+203C>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+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,158 control chromosomes in the GnomAD database, including 2,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.14 (2543 hom., cov: 33)
• Consequence: DRC4 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.353
• Publications: 3 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=-0.84).
• BP6: Variant 16-90022927-C-T is Benign according to our data. Variant chr16-90022927-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 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+203C>T		intron	N/A	NP_001472.1	O95995-1
	DRC4	NM_001286209.2		c.-73+3159C>T		intron	N/A	NP_001273138.1	O95995-2
	DRC4	NM_001286205.2		c.-370+203C>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+203C>T		intron	N/A	ENSP00000268699.4	O95995-1
	GAS8	ENST00000564853.1	TSL:1	n.55+203C>T		intron	N/A
	GAS8	ENST00000566266.5	TSL:1	n.3+203C>T		intron	N/A	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21658 AN: 152040 Hom.: 2532 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.142 AC: 21682 AN: 152158 Hom.: 2543 Cov.: 33 AF XY: 0.157 AC XY: 11666 AN XY: 74370

African (AFR) AF: 0.101 AC: 4196 AN: 41548

American (AMR) AF: 0.235 AC: 3595 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3468

East Asian (EAS) AF: 0.624 AC: 3201 AN: 5132

South Asian (SAS) AF: 0.159 AC: 765 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3057 AN: 10584

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6364 AN: 67982

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.0483 Hom.: 46

Bravo AF: 0.141

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	-0.84
CADD	Benign	9.6
DANN	Benign	0.95
PhyloP100		0.35
PromoterAI		0.031	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: rs59443037; hg19: chr16-90089335;