20-34534689-C-T

Variant names:

• chr20-34534689-C-T
• rs11537532
• NM_014183.4:c.141C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_014183.4(DYNLRB1):​c.141C>T​(p.His47His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,605,736 control chromosomes in the GnomAD database, including 17 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 0.0042 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (11 hom.)
• Consequence: DYNLRB1 NM_014183.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=3.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000495 (719/1453406) while in subpopulation AFR AF = 0.0165 (553/33436). AF 95% confidence interval is 0.0154. There are 11 homozygotes in GnomAdExome4. There are 321 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 642 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014183.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLRB1	NM_014183.4	MANE Select	c.141C>T	p.His47His	synonymous	Exon 3 of 4	NP_054902.1	Q9NP97-1
	DYNLRB1	NM_001319157.2		c.141C>T	p.His47His	synonymous	Exon 3 of 3	NP_001306086.1	B4DFR2
	DYNLRB1	NM_001382365.1		c.141C>T	p.His47His	synonymous	Exon 4 of 5	NP_001369294.1	Q9NP97-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLRB1	ENST00000357156.7	TSL:1 MANE Select	c.141C>T	p.His47His	synonymous	Exon 3 of 4	ENSP00000349679.2	Q9NP97-1
	ENSG00000289720	ENST00000696979.1		n.*248C>T		non_coding_transcript_exon	Exon 27 of 28	ENSP00000513014.1
	ENSG00000289720	ENST00000696979.1		n.*248C>T		3_prime_UTR	Exon 27 of 28	ENSP00000513014.1

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 640 AN: 152212 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00118 AC: 286 AN: 243034 AF XY: 0.000886

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.000911

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000457

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.000495 AC: 719 AN: 1453406 Hom.: 11 Cov.: 31 AF XY: 0.000444 AC XY: 321 AN XY: 722408

African (AFR) AF: 0.0165 AC: 553 AN: 33436

American (AMR) AF: 0.000949 AC: 42 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25334

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000165 AC: 14 AN: 84634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5730

European-Non Finnish (NFE) AF: 0.0000163 AC: 18 AN: 1107312

Other (OTH) AF: 0.00137 AC: 82 AN: 60058

GnomAD4 genome AF: 0.00421 AC: 642 AN: 152330 Hom.: 6 Cov.: 32 AF XY: 0.00381 AC XY: 284 AN XY: 74494

African (AFR) AF: 0.0145 AC: 601 AN: 41578

American (AMR) AF: 0.00209 AC: 32 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=73/27	polymorphism

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: rs11537532; hg19: chr20-33122493;