17-59573835-A-G

Position:

• chr17-59573835-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024612.5(DHX40):​c.642A>G​(p.Glu214Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,528 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (20 hom., cov: 29)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: DHX40 NM_024612.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.331

Genes affected

DHX40 (HGNC:18018): (DEAH-box helicase 40) This gene encodes a member of the DExH/D box family of ATP-dependent RNA helicases that have an essential role in RNA metabolism. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-59573835-A-G is Benign according to our data. Variant chr17-59573835-A-G is described in ClinVar as [Benign]. Clinvar id is 786951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.331 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00923 (1402/151958) while in subpopulation AFR AF= 0.0306 (1266/41420). AF 95% confidence interval is 0.0292. There are 20 homozygotes in gnomad4. There are 679 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1402 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX40	NM_024612.5	c.642A>G	p.Glu214Glu	synonymous_variant	5/18	ENST00000251241.9	NP_078888.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX40	ENST00000251241.9	c.642A>G	p.Glu214Glu	synonymous_variant	5/18	1	NM_024612.5	ENSP00000251241.4

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1401 AN: 151840 Hom.: 20 Cov.: 29

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00591

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00244 AC: 611 AN: 250604 Hom.: 11 AF XY: 0.00192 AC XY: 261 AN XY: 135636

Gnomad AFR exome AF: 0.0316

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00108 AC: 1577 AN: 1461570 Hom.: 28 Cov.: 31 AF XY: 0.000960 AC XY: 698 AN XY: 727098

Gnomad4 AFR exome AF: 0.0345

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome AF: 0.00923 AC: 1402 AN: 151958 Hom.: 20 Cov.: 29 AF XY: 0.00914 AC XY: 679 AN XY: 74272

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.00590

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0100

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.0109

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.9
DANN	Benign	0.60

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: rs143179414; hg19: chr17-57651196;