Genetic Variant NM_001366661.1:c.3684A>G (chr17-2691866-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001366661.1(CLUH):c.3684A>G(p.Glu1228Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,544,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CLUH
NM_001366661.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 17-2691866-T-C is Benign according to our data. Variant chr17-2691866-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 727262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.12 with no splicing effect.

BS2

High AC in GnomAd4 at 106 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	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUH	NM_001366661.1	MANE Select	c.3684A>G	p.Glu1228Glu	synonymous	Exon 24 of 26	NP_001353590.1	A0A494C0R8
CLUH	NM_015229.4		c.3681A>G	p.Glu1227Glu	synonymous	Exon 24 of 26	NP_056044.4
CLUH	NM_001366662.1		c.3567A>G	p.Glu1189Glu	synonymous	Exon 24 of 26	NP_001353591.1	O75153

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLUH	ENST00000651024.2	MANE Select	c.3684A>G	p.Glu1228Glu	synonymous	Exon 24 of 26	ENSP00000498679.1	A0A494C0R8
CLUH	ENST00000574210.5	TSL:1	n.1008A>G		non_coding_transcript_exon	Exon 8 of 9
CLUH	ENST00000876318.1		c.3702A>G	p.Glu1234Glu	synonymous	Exon 24 of 26	ENSP00000546377.1

Frequencies

GnomAD3 genomes

AF:

0.000707

AC:

107

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.00

Gnomad OTH

AF:

0.000483

GnomAD2 exomes

AF:

0.000101

AC:

AN:

148772

AF XY:

0.0000882

show subpopulations

Gnomad AFR exome

AF:

0.00176

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000661

AC:

AN:

1392794

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

687462

show subpopulations

African (AFR)

AF:

0.00257

AC:

AN:

31570

American (AMR)

AF:

0.0000840

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25098

East Asian (EAS)

AF:

0.00

AC:

AN:

35688

South Asian (SAS)

AF:

0.00

AC:

AN:

79306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43298

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078666

Other (OTH)

AF:

0.000121

AC:

AN:

57880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000700

AC:

106

AN:

151530

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.00242

AC:

100

AN:

41308

American (AMR)

AF:

0.000328

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67788

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000712

Hom.:

Bravo

AF:

0.000646

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.6

(source)

DANN

Benign

0.58

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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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