dbSNP rs2241039: DRC4:c.-73+2261G>A (chr16-90022029-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286209.2(DRC4):c.-73+2261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,938 control chromosomes in the GnomAD database, including 15,033 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15033 hom., cov: 32)

Exomes 𝑓: 0.29 ( 0 hom. )

Consequence

DRC4
NM_001286209.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

Publications

15 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DRC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001286209.2 link	c.-73+2261G>A		intron_variant	Intron 1 of 10		NP_001273138.1
DRC4	XM_011522992.3 link	c.-269+2261G>A		intron_variant	Intron 1 of 9		XP_011521294.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
GAS8	ENST00000536122.7 link	c.-73+2261G>A	intron_variant	Intron 1 of 10	2	ENSP00000440977.1
GAS8	ENST00000561675.1 link	c.-269+2261G>A	intron_variant	Intron 1 of 2	3	ENSP00000457554.1
GAS8	ENST00000563980.5 link	n.223-18G>A	intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66044

AN:

151804

Hom.:

15005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.439

GnomAD4 exome

AF:

0.286

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

AF:

0.435

AC:

66126

AN:

151924

Hom.:

15033

Cov.:

AF XY:

0.449

AC XY:

33338

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.407

AC:

16874

AN:

41410

American (AMR)

AF:

0.531

AC:

8108

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

997

AN:

3470

East Asian (EAS)

AF:

0.787

AC:

4074

AN:

5176

South Asian (SAS)

AF:

0.552

AC:

2655

AN:

4806

European-Finnish (FIN)

AF:

0.546

AC:

5758

AN:

10544

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26287

AN:

67946

Other (OTH)

AF:

0.444

AC:

936

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1811

3622

5433

7244

9055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.391

Hom.:

11046

Bravo

AF:

0.430

Asia WGS

AF:

0.639

AC:

2224

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.41

(source)

DANN

Benign

0.55

PhyloP100

-0.34

PromoterAI

-0.0036

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over