rs6120669

Variant names:

• chr20-34517223-T-C
• rs6120669
• NM_014183.4:c.3+762T>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.3+762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,038 control chromosomes in the GnomAD database, including 15,495 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 0.44 (15495 hom., cov: 32)
• Consequence: DYNLRB1 NM_014183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLRB1	NM_014183.4	c.3+762T>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.3+762T>C		intron_variant	Intron 1 of 3	1	NM_014183.4	ENSP00000349679.2
ENSG00000289720	ENST00000696979.1	n.*115-9049T>C		intron_variant	Intron 25 of 27			ENSP00000513014.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67202 AN: 151920 Hom.: 15500 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.442 AC: 67209 AN: 152038 Hom.: 15495 Cov.: 32 AF XY: 0.445 AC XY: 33074 AN XY: 74302

African (AFR) AF: 0.334 AC: 13833 AN: 41430

American (AMR) AF: 0.358 AC: 5468 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2043 AN: 5182

South Asian (SAS) AF: 0.425 AC: 2043 AN: 4810

European-Finnish (FIN) AF: 0.591 AC: 6236 AN: 10558

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34053 AN: 67994

Other (OTH) AF: 0.452 AC: 954 AN: 2112

Alfa AF: 0.454 Hom.: 5060

Bravo AF: 0.420

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.81
PhyloP100		0.15
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

Other links and lift over

dbSNP: rs6120669; hg19: chr20-33105028;