1-40257318-G-C

Position:

• chr1-40257318-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The ENST00000567508.2(ZMPSTE24-DT):​n.654C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,308 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZMPSTE24-DT ENST00000567508.2 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0560

Genes affected

ZMPSTE24-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0112 (1704/152308) while in subpopulation NFE AF= 0.0179 (1220/68026). AF 95% confidence interval is 0.0171. There are 20 homozygotes in gnomad4. There are 768 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.40257318G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24-DT	ENST00000567508.2	n.654C>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1704 AN: 152190 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0186

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0112 AC: 1704 AN: 152308 Hom.: 20 Cov.: 32 AF XY: 0.0103 AC XY: 768 AN XY: 74478

Gnomad4 AFR AF: 0.00315

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0118 Hom.: 1

Bravo AF: 0.0117

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

ZMPSTE24 homepage - Leiden Muscular Dystrophy pages

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147867849; hg19: chr1-40722990;