rs7218904

Positions:

• chr17-60404137-G-A
• chr17-60404137-G-C

Variant summary

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

The ENST00000461535.1(CHCT1):​c.-61+11595G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,112 control chromosomes in the GnomAD database, including 9,046 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 0.22 (9046 hom., cov: 32)
• Consequence: CHCT1 ENST00000461535.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

Genes affected

USP32 (HGNC:19143): (ubiquitin specific peptidase 32) Enables thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CHCT1 (HGNC:26990): (CHD1 helical C-terminal domain containing 1)

LOC105371850 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP32	XM_011525371.2	c.106+18109C>T		intron_variant			XP_011523673.1
USP32	XM_011525372.2	c.106+18109C>T		intron_variant			XP_011523674.1
LOC105371850	XR_007065870.1	n.179-1176C>T		intron_variant
LOC105371850	XR_934893.3	n.236-1176C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP32	ENST00000588898.1	c.106+18109C>T		intron_variant		5		ENSP00000467098.1
CHCT1	ENST00000461535.1	c.-61+11595G>A		intron_variant		2		ENSP00000468617.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33201 AN: 151994 Hom.: 9006 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33292 AN: 152112 Hom.: 9046 Cov.: 32 AF XY: 0.213 AC XY: 15841 AN XY: 74360

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0472

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.178

Alfa AF: 0.0892 Hom.: 574

Bravo AF: 0.247

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7218904; hg19: chr17-58481498;