rs1387330

Variant names:

• chr4-168408170-G-A
• rs1387330
• NM_001012967.3:c.2980-1464C>T

Variant summary

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

The NM_001012967.3(DDX60L):​c.2980-1464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,986 control chromosomes in the GnomAD database, including 9,009 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 0.34 (9009 hom., cov: 32)
• Consequence: DDX60L NM_001012967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX60L	NM_001012967.3	c.2980-1464C>T		intron_variant	Intron 22 of 37	ENST00000682922.1	NP_001012985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX60L	ENST00000682922.1	c.2980-1464C>T		intron_variant	Intron 22 of 37		NM_001012967.3	ENSP00000507872.1
DDX60L	ENST00000511577.5	c.2980-1464C>T		intron_variant	Intron 22 of 37	5		ENSP00000422423.1
DDX60L	ENST00000505890.5	c.2980-1464C>T		intron_variant	Intron 22 of 29	2		ENSP00000422202.1
DDX60L	ENST00000505863.1	c.2068-1464C>T		intron_variant	Intron 15 of 19	2		ENSP00000421026.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52336 AN: 151868 Hom.: 8995 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.345 AC: 52379 AN: 151986 Hom.: 9009 Cov.: 32 AF XY: 0.347 AC XY: 25800 AN XY: 74282

African (AFR) AF: 0.339 AC: 14035 AN: 41438

American (AMR) AF: 0.329 AC: 5025 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2180 AN: 5158

South Asian (SAS) AF: 0.415 AC: 2001 AN: 4822

European-Finnish (FIN) AF: 0.399 AC: 4215 AN: 10552

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22859 AN: 67956

Other (OTH) AF: 0.348 AC: 733 AN: 2108

Alfa AF: 0.341 Hom.: 37298

Bravo AF: 0.338

Asia WGS AF: 0.456 AC: 1582 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1387330; hg19: chr4-169329321;