1-40257946-G-A

Position:

• chr1-40257946-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000567508.2(ZMPSTE24-DT):​n.26C>T 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 0.0984 in 350,266 control chromosomes in the GnomAD database, including 1,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (902 hom., cov: 32)
  • Exomes 𝑓: 0.094 (1026 hom.)
• Consequence: ZMPSTE24-DT ENST00000567508.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.172

Genes affected

ZMPSTE24-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-40257946-G-A is Benign according to our data. Variant chr1-40257946-G-A is described in ClinVar as [Benign]. Clinvar id is 140505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40257946-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.40257946G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMPSTE24-DT	ENST00000567508.2	n.26C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15727 AN: 152126 Hom.: 900 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0419

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.0950

GnomAD4 exome AF: 0.0944 AC: 18700 AN: 198022 Hom.: 1026 Cov.: 3 AF XY: 0.0975 AC XY: 10162 AN XY: 104234

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.0559

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0850

Gnomad4 NFE exome AF: 0.0822

Gnomad4 OTH exome AF: 0.0894

GnomAD4 genome AF: 0.103 AC: 15757 AN: 152244 Hom.: 902 Cov.: 32 AF XY: 0.105 AC XY: 7797 AN XY: 74440

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.0983

Alfa AF: 0.0919 Hom.: 628

Bravo AF: 0.106

Asia WGS AF: 0.137 AC: 480 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	ZMPSTE24 homepage - Leiden Muscular Dystrophy pages	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3765483; hg19: chr1-40723618;