NM_014183.4:c.4-3227T>C

Variant names:

• chr20-34523041-T-C
• rs1122174
• NM_014183.4:c.4-3227T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014183.4(DYNLRB1):​c.4-3227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,188 control chromosomes in the GnomAD database, including 54,040 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 0.84 (54040 hom., cov: 31)
• Consequence: DYNLRB1 NM_014183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 10 publications found

Genes affected

DYNLRB1 (HGNC:15468): (dynein light chain roadblock-type 1) This gene is a member of the roadblock dynein light chain family. The encoded cytoplasmic protein is capable of binding intermediate chain proteins, interacts with transforming growth factor-beta, and has been implicated in the regulation of actin modulating proteins. Upregulation of this gene has been associated with hepatocellular carcinomas, suggesting that this gene may be involved in tumor progression. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 12 and 18. [provided by RefSeq, Aug 2013]

ENSG00000289720 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLRB1	NM_014183.4	c.4-3227T>C		intron_variant	Intron 1 of 3	ENST00000357156.7	NP_054902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLRB1	ENST00000357156.7	c.4-3227T>C		intron_variant	Intron 1 of 3	1	NM_014183.4	ENSP00000349679.2
ENSG00000289720	ENST00000696979.1	n.*115-3231T>C		intron_variant	Intron 25 of 27			ENSP00000513014.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127841 AN: 152070 Hom.: 53980 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.841 AC: 127961 AN: 152188 Hom.: 54040 Cov.: 31 AF XY: 0.842 AC XY: 62641 AN XY: 74398

African (AFR) AF: 0.865 AC: 35917 AN: 41516

American (AMR) AF: 0.895 AC: 13683 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3166 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4256 AN: 5174

South Asian (SAS) AF: 0.653 AC: 3152 AN: 4824

European-Finnish (FIN) AF: 0.874 AC: 9253 AN: 10582

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55589 AN: 68008

Other (OTH) AF: 0.865 AC: 1830 AN: 2116

Alfa AF: 0.827 Hom.: 188737

Bravo AF: 0.850

Asia WGS AF: 0.761 AC: 2644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1122174; hg19: chr20-33110846;