Variant 14-73689526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031427.4(DNAL1):c.532+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,586,552 control chromosomes in the GnomAD database, including 3,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 202 hom., cov: 31)

Exomes 𝑓: 0.061 ( 2909 hom. )

Consequence

DNAL1
NM_031427.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0360

Variant links:

Genes affected

DNAL1 (HGNC:23247): (dynein axonemal light chain 1) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

DNAL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 14-73689526-C-T is Benign according to our data. Variant chr14-73689526-C-T is described in ClinVar as [Benign]. Clinvar id is 163172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73689526-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DNAL1	NM_031427.4 linkuse as main transcript	c.532+11C>T	intron_variant	ENST00000553645.7
DNAL1	NM_001201366.2 linkuse as main transcript	c.415+11C>T	intron_variant
DNAL1	XM_017021679.3 linkuse as main transcript	c.415+11C>T	intron_variant
DNAL1	XM_024449715.2 linkuse as main transcript	c.415+11C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7 linkuse as main transcript	c.532+11C>T		intron_variant		1	NM_031427.4	P1	Q4LDG9-1

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7013

AN:

152042

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0553

Gnomad ASJ

AF:

0.0880

Gnomad EAS

AF:

0.0374

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0650

Gnomad OTH

AF:

0.0627

GnomAD3 exomes

AF:

0.0496

AC:

10282

AN:

207444

Hom.:

288

AF XY:

0.0501

AC XY:

5553

AN XY:

110738

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0347

Gnomad ASJ exome

AF:

0.0787

Gnomad EAS exome

AF:

0.0327

Gnomad SAS exome

AF:

0.0337

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0601

GnomAD4 exome

AF:

0.0615

AC:

88178

AN:

1434392

Hom.:

2909

Cov.:

AF XY:

0.0608

AC XY:

43164

AN XY:

710424

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0353

Gnomad4 ASJ exome

AF:

0.0812

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0376

Gnomad4 NFE exome

AF:

0.0675

Gnomad4 OTH exome

AF:

0.0606

GnomAD4 genome

AF:

0.0461

AC:

7008

AN:

152160

Hom.:

202

Cov.:

AF XY:

0.0443

AC XY:

3297

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0551

Gnomad4 ASJ

AF:

0.0880

Gnomad4 EAS

AF:

0.0375

Gnomad4 SAS

AF:

0.0321

Gnomad4 FIN

AF:

0.0374

Gnomad4 NFE

AF:

0.0650

Gnomad4 OTH

AF:

0.0620

Alfa

AF:

0.0437

Hom.:

Bravo

AF:

0.0464

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	415+11C>T in intron 8 of DNAL1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 6.5% (537/8256) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs72721725). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over