chr14-73689526-C-T

Variant names:

• chr14-73689526-C-T
• rs72721725
• NM_031427.4:c.532+11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0360

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.532+11C>T		intron_variant	Intron 7 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.415+11C>T		intron_variant	Intron 8 of 8		NP_001188295.1
DNAL1	XM_017021679.3	c.415+11C>T		intron_variant	Intron 8 of 8		XP_016877168.1
DNAL1	XM_024449715.2	c.415+11C>T		intron_variant	Intron 8 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.532+11C>T		intron_variant	Intron 7 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7013 AN: 152042 Hom.: 202 Cov.: 31

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

GnomAD2 exomes AF: 0.0496 AC: 10282 AN: 207444 AF XY: 0.0501

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 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.: 32 AF XY: 0.0608 AC XY: 43164 AN XY: 710424

Gnomad4 AFR exome AF: 0.0102 AC: 337 AN: 32980

Gnomad4 AMR exome AF: 0.0353 AC: 1421 AN: 40210

Gnomad4 ASJ exome AF: 0.0812 AC: 2075 AN: 25546

Gnomad4 EAS exome AF: 0.0290 AC: 1125 AN: 38788

Gnomad4 SAS exome AF: 0.0346 AC: 2821 AN: 81624

Gnomad4 FIN exome AF: 0.0376 AC: 1949 AN: 51864

Gnomad4 NFE exome AF: 0.0675 AC: 74173 AN: 1098112

Gnomad4 Remaining exome AF: 0.0606 AC: 3605 AN: 59530

GnomAD4 genome AF: 0.0461 AC: 7008 AN: 152160 Hom.: 202 Cov.: 31 AF XY: 0.0443 AC XY: 3297 AN XY: 74400

Gnomad4 AFR AF: 0.0119 AC: 0.0118698 AN: 0.0118698

Gnomad4 AMR AF: 0.0551 AC: 0.0550975 AN: 0.0550975

Gnomad4 ASJ AF: 0.0880 AC: 0.0879977 AN: 0.0879977

Gnomad4 EAS AF: 0.0375 AC: 0.0374517 AN: 0.0374517

Gnomad4 SAS AF: 0.0321 AC: 0.032131 AN: 0.032131

Gnomad4 FIN AF: 0.0374 AC: 0.0374433 AN: 0.0374433

Gnomad4 NFE AF: 0.0650 AC: 0.064975 AN: 0.064975

Gnomad4 OTH AF: 0.0620 AC: 0.0620265 AN: 0.0620265

Alfa AF: 0.0437 Hom.: 81

Bravo AF: 0.0464

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 16 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.69
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

Publications

LitVar

Other links and lift over

dbSNP: rs72721725; hg19: chr14-74156229;