rs2301659

chr19-18924545-G-T

Variant summary

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

The NM_019070.5(DDX49):c.853-78G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,498,574 control chromosomes in the GnomAD database, including 148,948 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 0.37 (12319 hom., cov: 32)
  • Exomes 𝑓: 0.44 (136629 hom.)
• Consequence: DDX49 NM_019070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

Genes affected

DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX49	NM_019070.5	c.853-78G>T		intron_variant		ENST00000247003.9
DDX49	XM_011528084.4	c.532-78G>T		intron_variant
DDX49	NR_033677.2	n.809-78G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX49	ENST00000247003.9	c.853-78G>T		intron_variant		1	NM_019070.5	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55955 AN: 151752 Hom.: 12313 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.443 AC: 596386 AN: 1346704 Hom.: 136629 AF XY: 0.440 AC XY: 297505 AN XY: 675984

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.369 AC: 55965 AN: 151870 Hom.: 12319 Cov.: 32 AF XY: 0.369 AC XY: 27370 AN XY: 74188

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.433

Alfa AF: 0.427 Hom.: 3039

Bravo AF: 0.372

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.67

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: rs2301659; hg19: chr19-19035354; COSMIC: COSV55358658; COSMIC: COSV55358658;