Genetic Variant NM_001481.3:c.3+6C>G (chr16-90022730-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Variant links:

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

DRC4 links:

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ACMG classification

Classification was made for transcript

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).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRC4	NM_001481.3	MANE Select	c.3+6C>G	splice_region intron	N/A	NP_001472.1	O95995-1
DRC4	NM_001286209.2		c.-73+2962C>G	intron	N/A	NP_001273138.1	O95995-2
DRC4	NM_001286205.2		c.-370+6C>G	splice_region intron	N/A	NP_001273134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAS8	ENST00000268699.9	TSL:1 MANE Select	c.3+6C>G	splice_region intron	N/A	ENSP00000268699.4	O95995-1
GAS8	ENST00000564853.1	TSL:1	n.55+6C>G	splice_region intron	N/A
GAS8	ENST00000566266.5	TSL:1	n.3+6C>G	splice_region intron	N/A	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

65314

AF XY:

0.0000266

show subpopulations

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:

AN:

1263380

Hom.:

Cov.:

AF XY:

0.00000324

AC XY:

AN XY:

616480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26052

American (AMR)

AF:

0.00

AC:

AN:

24074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21320

East Asian (EAS)

AF:

0.00

AC:

AN:

28588

South Asian (SAS)

AF:

0.0000298

AC:

AN:

67106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1009988

Other (OTH)

AF:

0.00

AC:

AN:

51660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.9

(source)

DANN

Benign

0.83

PhyloP100

-0.45

PromoterAI

-0.19

Neutral

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over