chr4-168493278-G-T

Variant names:

• chr4-168493278-G-T
• rs6819953
• ENST00000505150.5:n.289-393C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512958.1(DDX60L):​n.238-393C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,210 control chromosomes in the GnomAD database, including 735 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 0.092 (735 hom., cov: 32)
• Consequence: DDX60L ENST00000512958.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 4 publications found

Genes affected

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

LOC107986198 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512958.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60L	ENST00000505150.5	TSL:5	n.289-393C>A		intron	N/A
	DDX60L	ENST00000512958.1	TSL:3	n.238-393C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13977 AN: 152092 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0836

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0919 AC: 13993 AN: 152210 Hom.: 735 Cov.: 32 AF XY: 0.0939 AC XY: 6991 AN XY: 74426

African (AFR) AF: 0.122 AC: 5047 AN: 41538

American (AMR) AF: 0.0554 AC: 847 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 282 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5174

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0817 AC: 5553 AN: 67994

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.0816 Hom.: 988

Bravo AF: 0.0865

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.59
PhyloP100		0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6819953; hg19: chr4-169414429;