Variant chr17-2691601-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001366661.1(CLUH):c.3863+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,611,172 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 33 hom. )

Consequence

CLUH
NM_001366661.1 splice_region, intron

Scores

Splicing: ADA: 0.0001004

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0670

Variant links:

Genes affected

CLUH (HGNC:29094): (clustered mitochondria homolog) Enables mRNA binding activity. Involved in intracellular distribution of mitochondria. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CLUH links:

CLUH (HGNC:):

CLUH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-2691601-G-A is Benign according to our data. Variant chr17-2691601-G-A is described in ClinVar as [Benign]. Clinvar id is 784665.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0091 (1385/152252) while in subpopulation AFR AF= 0.0318 (1321/41556). AF 95% confidence interval is 0.0304. There are 23 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUH	NM_001366661.1 linkuse as main transcript	c.3863+8C>T		splice_region_variant, intron_variant		ENST00000651024.2	NP_001353590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUH	ENST00000651024.2 linkuse as main transcript	c.3863+8C>T		splice_region_variant, intron_variant			NM_001366661.1	ENSP00000498679.1		A0A494C0R8

Frequencies

GnomAD3 genomes

AF:

0.00908

AC:

1382

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00214

AC:

522

AN:

243692

Hom.:

AF XY:

0.00175

AC XY:

232

AN XY:

132934

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.000506

GnomAD4 exome

AF:

0.000986

AC:

1439

AN:

1458920

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

653

AN XY:

725732

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000864

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.00910

AC:

1385

AN:

152252

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0318

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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