rs114223887

chr14-73689328-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031427.4(DNAL1):c.392-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,547,294 control chromosomes in the GnomAD database, including 2,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (178 hom., cov: 30)
  • Exomes 𝑓: 0.052 (2065 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 14-73689328-G-A is Benign according to our data. Variant chr14-73689328-G-A is described in ClinVar as [Benign]. Clinvar id is 261959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL1	NM_031427.4	c.392-47G>A		intron_variant		ENST00000553645.7
DNAL1	NM_001201366.2	c.275-47G>A		intron_variant
DNAL1	XM_017021679.3	c.275-47G>A		intron_variant
DNAL1	XM_024449715.2	c.275-47G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7	c.392-47G>A		intron_variant		1	NM_031427.4	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7051 AN: 152062 Hom.: 177 Cov.: 30

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0536

GnomAD3 exomes AF: 0.0410 AC: 6390 AN: 155768 Hom.: 174 AF XY: 0.0430 AC XY: 3547 AN XY: 82478

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.0263

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.000184

Gnomad SAS exome AF: 0.0536

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0527

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0520 AC: 72484 AN: 1395114 Hom.: 2065 Cov.: 31 AF XY: 0.0524 AC XY: 36019 AN XY: 687558

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.0287

Gnomad4 ASJ exome AF: 0.0369

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.0547

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.0464 AC: 7055 AN: 152180 Hom.: 178 Cov.: 30 AF XY: 0.0455 AC XY: 3386 AN XY: 74406

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0517

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0473 Hom.: 39

Bravo AF: 0.0451

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.55
Dann	Benign	0.85

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: rs114223887; hg19: chr14-74156031;