19-47352883-G-C

Position:

• chr19-47352883-G-C

Variant summary

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

The NM_014681.6(DHX34):​c.-148G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,428,140 control chromosomes in the GnomAD database, including 23,519 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 0.24 (6668 hom., cov: 32)
  • Exomes 𝑓: 0.13 (16851 hom.)
• Consequence: DHX34 NM_014681.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

DHX34 (HGNC:16719): (DExH-box helicase 34) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX34	NM_014681.6	c.-148G>C		5_prime_UTR_variant	2/17	ENST00000328771.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX34	ENST00000328771.9	c.-148G>C		5_prime_UTR_variant	2/17	5	NM_014681.6	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36643 AN: 151922 Hom.: 6657 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.132 AC: 168114 AN: 1276100 Hom.: 16851 Cov.: 27 AF XY: 0.135 AC XY: 83367 AN XY: 619260

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0976

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.241 AC: 36690 AN: 152040 Hom.: 6668 Cov.: 32 AF XY: 0.243 AC XY: 18089 AN XY: 74332

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.221

Alfa AF: 0.115 Hom.: 912

Bravo AF: 0.261

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.089
DANN	Benign	0.42

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: rs1064202; hg19: chr19-47856140; COSMIC: COSV60896327;