rs140652745

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016222.4(DDX41):c.1683C>T(p.Pro561Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,448 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 13 hom. )

Consequence

DDX41
NM_016222.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.52

Variant links:

Genes affected

DDX41 (HGNC:18674): (DEAD-box helicase 41) 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD box protein family and interacts with several spliceosomal proteins. In addition, the encoded protein may recognize the bacterial second messengers cyclic di-GMP and cyclic di-AMP, resulting in the induction of genes involved in the innate immune response. [provided by RefSeq, Jan 2017]

DDX41 links:

DDX41 (HGNC:):

DDX41 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 5-177512145-G-A is Benign according to our data. Variant chr5-177512145-G-A is described in ClinVar as [Benign]. Clinvar id is 434912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.52 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00642 (978/152230) while in subpopulation AFR AF= 0.0225 (936/41530). AF 95% confidence interval is 0.0213. There are 13 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 978 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX41	NM_016222.4 linkuse as main transcript	c.1683C>T	p.Pro561Pro	synonymous_variant	16/17	ENST00000330503.12	NP_057306.2
DDX41	NM_001321732.2 linkuse as main transcript	c.1305C>T	p.Pro435Pro	synonymous_variant	15/16		NP_001308661.1
DDX41	NM_001321830.2 linkuse as main transcript	c.1305C>T	p.Pro435Pro	synonymous_variant	16/17		NP_001308759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX41	ENST00000330503.12 linkuse as main transcript	c.1683C>T	p.Pro561Pro	synonymous_variant	16/17	1	NM_016222.4	ENSP00000330349.8		Q9UJV9

Frequencies

GnomAD3 genomes

AF:

0.00642

AC:

977

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00189

AC:

472

AN:

249824

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.0260

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000712

AC:

1041

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

452

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.0242

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00642

AC:

978

AN:

152230

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

453

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00760

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 28, 2016

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.057

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over