rs4072407

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145038.5(DRC1):c.1397-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,612,870 control chromosomes in the GnomAD database, including 496,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 37103 hom., cov: 33)

Exomes 𝑓: 0.78 ( 459891 hom. )

Consequence

DRC1
NM_145038.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.30

Publications

8 publications found

Variant links:

Genes affected

DRC1 (HGNC:24245): (dynein regulatory complex subunit 1) This gene encodes a central component of the nexin-dynein complex (N-DRC), which regulates the assembly of ciliary dynein. Mutations in this gene can cause ciliary dyskinesia. [provided by RefSeq, Aug 2015]

DRC1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 21
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 80
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 2-26448676-A-G is Benign according to our data. Variant chr2-26448676-A-G is described in ClinVar as [Benign]. Clinvar id is 262565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5 link	c.1397-15A>G		intron_variant	Intron 10 of 16	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 link	c.377-15A>G		intron_variant	Intron 3 of 9		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 link	c.1397-15A>G	intron_variant	Intron 10 of 16	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000439066.2 link	n.127-15A>G	intron_variant	Intron 1 of 4	3
DRC1	ENST00000649059.1 link	n.*360-15A>G	intron_variant	Intron 9 of 15			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

101014

AN:

152044

Hom.:

37097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.872

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.825

Gnomad OTH

AF:

0.695

GnomAD2 exomes

AF:

0.714

AC:

179396

AN:

251128

AF XY:

0.733

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.816

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.903

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.768

GnomAD4 exome

AF:

0.783

AC:

1143533

AN:

1460708

Hom.:

459891

Cov.:

AF XY:

0.784

AC XY:

570023

AN XY:

726662

show subpopulations

African (AFR)

AF:

0.354

AC:

11842

AN:

33438

American (AMR)

AF:

0.576

AC:

25736

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

21105

AN:

26134

East Asian (EAS)

AF:

0.240

AC:

9544

AN:

39686

South Asian (SAS)

AF:

0.735

AC:

63362

AN:

86230

European-Finnish (FIN)

AF:

0.897

AC:

47929

AN:

53412

Middle Eastern (MID)

AF:

0.739

AC:

4250

AN:

5752

European-Non Finnish (NFE)

AF:

0.823

AC:

914477

AN:

1111022

Other (OTH)

AF:

0.751

AC:

45288

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12170

24340

36511

48681

60851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.664

AC:

101047

AN:

152162

Hom.:

37103

Cov.:

AF XY:

0.666

AC XY:

49579

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.374

AC:

15527

AN:

41480

American (AMR)

AF:

0.628

AC:

9607

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2846

AN:

3468

East Asian (EAS)

AF:

0.264

AC:

1364

AN:

5170

South Asian (SAS)

AF:

0.722

AC:

3480

AN:

4818

European-Finnish (FIN)

AF:

0.904

AC:

9591

AN:

10606

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.826

AC:

56148

AN:

68014

Other (OTH)

AF:

0.697

AC:

1473

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1427

2855

4282

5710

7137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.769

Hom.:

177535

Bravo

AF:

0.625

Asia WGS

AF:

0.573

AC:

1989

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 21

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0060

(source)

DANN

Benign

0.26

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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rs4072407

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over