rs311683

Positions:

• chr6-73417218-G-A
• chr6-73417218-G-T

Variant summary

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

The NM_018665.3(DDX43):​c.*57G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,900 control chromosomes in the GnomAD database, including 18,729 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 0.49 (18729 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DDX43 NM_018665.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

Genes affected

DDX43 (HGNC:18677): (DEAD-box helicase 43) The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD-box family and displays tumor-specific expression. [provided by RefSeq, Jul 2008]

CGAS (HGNC:21367): (cyclic GMP-AMP synthase) Enables several functions, including 2',3'-cyclic GMP-AMP synthase activity; chromatin binding activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including cellular response to exogenous dsRNA; positive regulation of intracellular signal transduction; and regulation of defense response. Located in several cellular components, including cytosol; nucleus; and site of double-strand break. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX43	NM_018665.3	c.*57G>A		3_prime_UTR_variant	17/17	ENST00000370336.5	NP_061135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX43	ENST00000370336.5	c.*57G>A		3_prime_UTR_variant	17/17	1	NM_018665.3	ENSP00000359361.4
CGAS	ENST00000370318.5	c.1333-3197C>T		intron_variant		1		ENSP00000359342.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74063 AN: 151782 Hom.: 18733 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.499

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.488 AC: 74084 AN: 151900 Hom.: 18729 Cov.: 32 AF XY: 0.492 AC XY: 36526 AN XY: 74192

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.503

Alfa AF: 0.527 Hom.: 21989

Bravo AF: 0.472

Asia WGS AF: 0.532 AC: 1852 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs311683; hg19: chr6-74126941;