rs12161908

Positions:

• chr14-101988573-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001376.5(DYNC1H1):​c.2719-130G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,173,818 control chromosomes in the GnomAD database, including 119 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 0.0059 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (102 hom.)
• Consequence: DYNC1H1 NM_001376.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0059 (899/152294) while in subpopulation EAS AF= 0.0367 (190/5182). AF 95% confidence interval is 0.0324. There are 17 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 899 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1H1	NM_001376.5	c.2719-130G>C		intron_variant		ENST00000360184.10	NP_001367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1H1	ENST00000360184.10	c.2719-130G>C		intron_variant		1	NM_001376.5	ENSP00000348965	P1

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 887 AN: 152176 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00441 AC: 4508 AN: 1021524 Hom.: 102 AF XY: 0.00440 AC XY: 2288 AN XY: 519600

Gnomad4 AFR exome AF: 0.00283

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.000975

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.00590 AC: 899 AN: 152294 Hom.: 17 Cov.: 32 AF XY: 0.00646 AC XY: 481 AN XY: 74470

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00281 Hom.: 3

Bravo AF: 0.00769

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.39

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: rs12161908; hg19: chr14-102454910;