rs941793

Variant names:

• chr14-102041124-A-G
• rs941793
• NM_001376.5:c.11942-450A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376.5(DYNC1H1):​c.11942-450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 338,510 control chromosomes in the GnomAD database, including 18,938 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 0.35 (12362 hom., cov: 32)
  • Exomes 𝑓: 0.25 (6576 hom.)
• Consequence: DYNC1H1 NM_001376.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

Genes affected

DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

ENSG00000258959 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1H1	NM_001376.5	c.11942-450A>G		intron_variant	Intron 64 of 77	ENST00000360184.10	NP_001367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC1H1	ENST00000360184.10	c.11942-450A>G		intron_variant	Intron 64 of 77	1	NM_001376.5	ENSP00000348965.4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53803 AN: 151910 Hom.: 12322 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.248 AC: 46322 AN: 186482 Hom.: 6576 Cov.: 0 AF XY: 0.249 AC XY: 24972 AN XY: 100452

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.355 AC: 53904 AN: 152028 Hom.: 12362 Cov.: 32 AF XY: 0.349 AC XY: 25964 AN XY: 74312

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.355

Alfa AF: 0.276 Hom.: 1767

Bravo AF: 0.373

Asia WGS AF: 0.285 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.49

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: rs941793; hg19: chr14-102507461;