rs78923296

Variant names:

• chr5-177511717-G-A
• rs78923296
• NM_016222.4:c.*74C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016222.4(DDX41):​c.*74C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000941 in 1,586,982 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (11 hom.)
• Consequence: DDX41 NM_016222.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.213

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-177511717-G-A is Benign according to our data. Variant chr5-177511717-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00452 (688/152344) while in subpopulation AFR AF = 0.0158 (658/41574). AF 95% confidence interval is 0.0148. There are 2 homozygotes in GnomAd4. There are 337 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 688 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX41	NM_016222.4	c.*74C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000330503.12	NP_057306.2
DDX41	NM_001321732.2	c.*74C>T		3_prime_UTR_variant	Exon 16 of 16		NP_001308661.1
DDX41	NM_001321830.2	c.*74C>T		3_prime_UTR_variant	Exon 17 of 17		NP_001308759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX41	ENST00000330503	c.*74C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_016222.4	ENSP00000330349.8

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 689 AN: 152226 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000561 AC: 805 AN: 1434638 Hom.: 11 Cov.: 31 AF XY: 0.000470 AC XY: 334 AN XY: 710552

Gnomad4 AFR exome AF: 0.0199 AC: 659 AN: 33068

Gnomad4 AMR exome AF: 0.00100 AC: 44 AN: 43910

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 24916

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39284

Gnomad4 SAS exome AF: 0.0000715 AC: 6 AN: 83906

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52260

Gnomad4 NFE exome AF: 0.0000156 AC: 17 AN: 1092458

Gnomad4 Remaining exome AF: 0.00128 AC: 76 AN: 59178

GnomAD4 genome AF: 0.00452 AC: 688 AN: 152344 Hom.: 2 Cov.: 33 AF XY: 0.00452 AC XY: 337 AN XY: 74500

Gnomad4 AFR AF: 0.0158 AC: 0.0158272 AN: 0.0158272

Gnomad4 AMR AF: 0.00131 AC: 0.00130685 AN: 0.00130685

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000621633 AN: 0.000621633

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000147011 AN: 0.0000147011

Gnomad4 OTH AF: 0.00284 AC: 0.00283554 AN: 0.00283554

Alfa AF: 0.00198 Hom.: 1

Bravo AF: 0.00491

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 21, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 06, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.66
Mutation Taster		=100/0	polymorphism

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: rs78923296; hg19: chr5-176938718;