19-18926244-T-C

Variant names:

• chr19-18926244-T-C
• rs2301661
• NM_019070.5:c.1028-59T>C

Variant summary

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

The NM_019070.5(DDX49):​c.1028-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,524,494 control chromosomes in the GnomAD database, including 168,055 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 0.43 (15090 hom., cov: 33)
  • Exomes 𝑓: 0.47 (152965 hom.)
• Consequence: DDX49 NM_019070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 15 publications found

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]

ENSG00000268193 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX49	NM_019070.5	c.1028-59T>C		intron_variant	Intron 9 of 12	ENST00000247003.9	NP_061943.2
DDX49	NR_033677.2	n.984-59T>C		intron_variant	Intron 9 of 12
DDX49	XM_011528084.4	c.707-59T>C		intron_variant	Intron 10 of 13		XP_011526386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX49	ENST00000247003.9	c.1028-59T>C		intron_variant	Intron 9 of 12	1	NM_019070.5	ENSP00000247003.3
ENSG00000268193	ENST00000596918.5	n.*167+5081A>G		intron_variant	Intron 4 of 6	5		ENSP00000469669.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65806 AN: 151984 Hom.: 15069 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.467 AC: 641355 AN: 1372392 Hom.: 152965 AF XY: 0.464 AC XY: 314565 AN XY: 677606

African (AFR) AF: 0.335 AC: 10465 AN: 31242

American (AMR) AF: 0.584 AC: 20676 AN: 35420

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 15106 AN: 24612

East Asian (EAS) AF: 0.219 AC: 7848 AN: 35758

South Asian (SAS) AF: 0.353 AC: 27560 AN: 78172

European-Finnish (FIN) AF: 0.398 AC: 19508 AN: 49004

Middle Eastern (MID) AF: 0.588 AC: 3311 AN: 5628

European-Non Finnish (NFE) AF: 0.484 AC: 510339 AN: 1055416

Other (OTH) AF: 0.465 AC: 26542 AN: 57140

GnomAD4 genome AF: 0.433 AC: 65865 AN: 152102 Hom.: 15090 Cov.: 33 AF XY: 0.428 AC XY: 31810 AN XY: 74354

African (AFR) AF: 0.338 AC: 14020 AN: 41482

American (AMR) AF: 0.556 AC: 8503 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3472

East Asian (EAS) AF: 0.188 AC: 971 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4830

European-Finnish (FIN) AF: 0.391 AC: 4141 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32817 AN: 67962

Other (OTH) AF: 0.476 AC: 1004 AN: 2110

Alfa AF: 0.482 Hom.: 28657

Bravo AF: 0.443

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-1.6
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: rs2301661; hg19: chr19-19037053; COSMIC: COSV55356497; COSMIC: COSV55356497;