Genetic Variant CLUH:c.3863+8C>T (chr17-2691601-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1385 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366661.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLUH	NM_001366661.1	MANE Select	c.3863+8C>T	splice_region intron	N/A	NP_001353590.1	A0A494C0R8
CLUH	NM_015229.4		c.3860+8C>T	splice_region intron	N/A	NP_056044.4
CLUH	NM_001366662.1		c.3746+8C>T	splice_region intron	N/A	NP_001353591.1	O75153

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLUH	ENST00000651024.2	MANE Select	c.3863+8C>T	splice_region intron	N/A	ENSP00000498679.1	A0A494C0R8
CLUH	ENST00000574210.5	TSL:1	n.1195C>T	non_coding_transcript_exon	Exon 9 of 9
CLUH	ENST00000876318.1		c.3881+8C>T	splice_region intron	N/A	ENSP00000546377.1

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

GnomAD2 exomes

AF:

0.00214

AC:

522

AN:

243692

AF XY:

0.00175

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 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

African (AFR)

AF:

0.0344

AC:

1150

AN:

33426

American (AMR)

AF:

0.00173

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52696

Middle Eastern (MID)

AF:

0.000703

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000864

AC:

AN:

1110692

Other (OTH)

AF:

0.00178

AC:

107

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00910

AC:

1385

AN:

152252

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0318

AC:

1321

AN:

41556

American (AMR)

AF:

0.00307

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68016

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

128

191

255

319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

(source)

DANN

Benign

0.68

PhyloP100

-0.067

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over