17-2695345-C-G

Position:

• chr17-2695345-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUH	NM_001366661.1	c.2544+29G>C		intron_variant		ENST00000651024.2	NP_001353590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUH	ENST00000651024.2	c.2544+29G>C		intron_variant			NM_001366661.1	ENSP00000498679.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76388 AN: 152112 Hom.: 21180 Cov.: 35

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

GnomAD3 exomes AF: 0.574 AC: 142627 AN: 248464 Hom.: 42213 AF XY: 0.579 AC XY: 78084 AN XY: 134896

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 SAS exome AF: 0.598

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.: 66 AF XY: 0.604 AC XY: 438973 AN XY: 726702

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.642

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.502 AC: 76416 AN: 152230 Hom.: 21192 Cov.: 35 AF XY: 0.500 AC XY: 37231 AN XY: 74416

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.517

Alfa AF: 0.581 Hom.: 4975

Bravo AF: 0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs1003399; hg19: chr17-2598639; COSMIC: COSV70927792; COSMIC: COSV70927792;