NM_004397.6:c.1175-4delT

Variant names:

• chr11-118755506-TA-T
• rs551201488
• NM_004397.6:c.1175-4delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004397.6(DDX6):​c.1175-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,160,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: DDX6 NM_004397.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

Genes affected

DDX6 (HGNC:2747): (DEAD-box helicase 6) This gene encodes a member of the DEAD box protein family. The protein is an RNA helicase found in P-bodies and stress granules, and functions in translation suppression and mRNA degradation. It is required for microRNA-induced gene silencing. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0193 (19569/1013454) while in subpopulation AFR AF= 0.0217 (495/22782). AF 95% confidence interval is 0.0201. There are 0 homozygotes in gnomad4_exome. There are 9452 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1175-4delT		splice_region_variant, intron_variant	Intron 11 of 13	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1175-4delT		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1175-4delT		splice_region_variant, intron_variant	Intron 11 of 12	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1175-4delT		splice_region_variant, intron_variant	Intron 11 of 13	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.778-4delT		splice_region_variant, intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.000334 AC: 49 AN: 146848 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000408

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0193 AC: 19569 AN: 1013454 Hom.: 0 Cov.: 18 AF XY: 0.0187 AC XY: 9452 AN XY: 504812

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.00955

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.0184

GnomAD4 genome AF: 0.000333 AC: 49 AN: 146934 Hom.: 0 Cov.: 32 AF XY: 0.000462 AC XY: 33 AN XY: 71422

Gnomad4 AFR AF: 0.000744

Gnomad4 AMR AF: 0.000407

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000109

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0322 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs551201488; hg19: chr11-118626215;