Genetic Variant NM_001366661.1:c.2544+29G>C (chr17-2695345-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001366661.1(CLUH):c.2544+29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,068 control chromosomes in the GnomAD database, including 290,661 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 0.50 ( 21192 hom., cov: 35)

Exomes 𝑓: 0.60 ( 269469 hom. )

Consequence

CLUH
NM_001366661.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

15 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

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.2544+29G>C	intron	N/A	NP_001353590.1	A0A494C0R8
CLUH	NM_015229.4		c.2541+29G>C	intron	N/A	NP_056044.4
CLUH	NM_001366662.1		c.2427+29G>C	intron	N/A	NP_001353591.1	O75153

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLUH	ENST00000651024.2	MANE Select	c.2544+29G>C	intron	N/A	ENSP00000498679.1	A0A494C0R8
CLUH	ENST00000876318.1		c.2562+29G>C	intron	N/A	ENSP00000546377.1
CLUH	ENST00000876317.1		c.2559+29G>C	intron	N/A	ENSP00000546376.1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76388

AN:

152112

Hom.:

21180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.516

GnomAD2 exomes

AF:

0.574

AC:

142627

AN:

248464

AF XY:

0.579

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.648

Gnomad ASJ exome

AF:

0.645

Gnomad EAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.585

GnomAD4 exome

AF:

0.603

AC:

881404

AN:

1460838

Hom.:

269469

Cov.:

AF XY:

0.604

AC XY:

438973

AN XY:

726702

show subpopulations

African (AFR)

AF:

0.228

AC:

7644

AN:

33472

American (AMR)

AF:

0.642

AC:

28713

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

16901

AN:

26120

East Asian (EAS)

AF:

0.530

AC:

21049

AN:

39686

South Asian (SAS)

AF:

0.603

AC:

52010

AN:

86244

European-Finnish (FIN)

AF:

0.496

AC:

26186

AN:

52780

Middle Eastern (MID)

AF:

0.581

AC:

3351

AN:

5768

European-Non Finnish (NFE)

AF:

0.621

AC:

690867

AN:

1111720

Other (OTH)

AF:

0.575

AC:

34683

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

21496

42992

64488

85984

107480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18384

36768

55152

73536

91920

<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:

0.502

AC:

76416

AN:

152230

Hom.:

21192

Cov.:

AF XY:

0.500

AC XY:

37231

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.249

AC:

10352

AN:

41544

American (AMR)

AF:

0.605

AC:

9254

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2240

AN:

3468

East Asian (EAS)

AF:

0.495

AC:

2555

AN:

5160

South Asian (SAS)

AF:

0.584

AC:

2815

AN:

4822

European-Finnish (FIN)

AF:

0.478

AC:

5076

AN:

10610

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.622

AC:

42316

AN:

68014

Other (OTH)

AF:

0.517

AC:

1093

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1848

3695

5543

7390

9238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.581

Hom.:

4975

Bravo

AF:

0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.12

(source)

DANN

Benign

0.43

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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