Variant rs1045481 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015721.3(GEMIN4):c.3126C>T(p.Ile1042Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,264 control chromosomes in the GnomAD database, including 46,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3261 hom., cov: 34)

Exomes 𝑓: 0.24 ( 43381 hom. )

Consequence

GEMIN4
NM_015721.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.235

Variant links:

Genes affected

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]

GEMIN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-744917-G-A is Benign according to our data. Variant chr17-744917-G-A is described in ClinVar as [Benign]. Clinvar id is 3057158.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.235 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN4	NM_015721.3 link	c.3126C>T	p.Ile1042Ile	synonymous_variant	Exon 2 of 2	ENST00000319004.6	NP_056536.2	P57678Q8WUM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN4	ENST00000319004.6 link	c.3126C>T	p.Ile1042Ile	synonymous_variant	Exon 2 of 2	1	NM_015721.3	ENSP00000321706.5		P57678
GEMIN4	ENST00000576778.1 link	c.3093C>T	p.Ile1031Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000459565.1		I3L2C7

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29026

AN:

152152

Hom.:

3259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0909

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.204

AC:

50474

AN:

247916

Hom.:

5637

AF XY:

0.208

AC XY:

28034

AN XY:

134660

show subpopulations

Gnomad AFR exome

AF:

0.0906

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.239

AC:

349395

AN:

1460994

Hom.:

43381

Cov.:

AF XY:

0.238

AC XY:

173113

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.0854

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.191

AC:

29033

AN:

152270

Hom.:

3261

Cov.:

AF XY:

0.189

AC XY:

14066

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.230

Hom.:

5701

Bravo

AF:

0.184

Asia WGS

AF:

0.188

AC:

658

AN:

3478

EpiCase

AF:

0.248

EpiControl

AF:

0.251

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GEMIN4-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.12

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over