17-752680-G-A

Position:

• chr17-752680-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_024120.2(DBIL5P):​n.348G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 981,524 control chromosomes in the GnomAD database, including 32,060 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 0.20 (3567 hom., cov: 33)
  • Exomes 𝑓: 0.26 (28493 hom.)
• Consequence: DBIL5P NR_024120.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

Genes affected

(HGNC:):

GEMIN4 (HGNC:15717): (gem nuclear organelle associated protein 4) The product of this gene is part of a large complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini bodies (gems). The complex functions in spliceosomal snRNP assembly in the cytoplasm, and regenerates spliceosomes required for pre-mRNA splicing in the nucleus. The encoded protein directly interacts with a DEAD box protein and several spliceosome core proteins. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBIL5P	NR_024120.2	n.348G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000536214.1	n.21G>A		non_coding_transcript_exon_variant	1/1
GEMIN4	ENST00000570364.5	c.-137C>T		5_prime_UTR_variant	1/3	3
GEMIN4	ENST00000576383.1	c.-24+1279C>T		intron_variant		3
	ENST00000449830.5	n.14G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30209 AN: 152070 Hom.: 3565 Cov.: 33

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.257 AC: 213018 AN: 829336 Hom.: 28493 Cov.: 14 AF XY: 0.256 AC XY: 98662 AN XY: 384974

Gnomad4 AFR exome AF: 0.0768

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.199 AC: 30215 AN: 152188 Hom.: 3567 Cov.: 33 AF XY: 0.196 AC XY: 14563 AN XY: 74384

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.215

Alfa AF: 0.253 Hom.: 7216

Bravo AF: 0.192

Asia WGS AF: 0.189 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.3
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs910924; hg19: chr17-655920;