1-40257318-G-C

Variant names:

• chr1-40257318-G-C
• rs147867849
• ENST00000567508.3:n.677C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The ENST00000567508.3(ZMPSTE24-DT):​n.677C>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 ENST00000567508.3 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0560
• Publications: 0 publications found

Genes affected

ZMPSTE24-DT (HGNC:55402): (ZMPSTE24 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24-DT	ENST00000567508.3	n.677C>G		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00315 AC: 131 AN: 41570

American (AMR) AF: 0.0144 AC: 220 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0179 AC: 1220 AN: 68026

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

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

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ZMPSTE24 homepage - Leiden Muscular Dystrophy pages

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		0.056
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs147867849; hg19: chr1-40722990;