1-40257750-C-G

Variant names:

• chr1-40257750-C-G
• rs11811211
• ENST00000567508.3:n.245G>C

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.245G>C 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 0.012 in 159,360 control chromosomes in the GnomAD database, including 46 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 0.012 (46 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: ZMPSTE24-DT ENST00000567508.3 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.164
• Publications: 2 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=-0.78).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1901/152320) while in subpopulation AFR AF = 0.0437 (1818/41566). AF 95% confidence interval is 0.0421. There are 46 homozygotes in GnomAd4. There are 883 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 46 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.245G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1893 AN: 152202 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.000710 AC: 5 AN: 7040 Hom.: 0 Cov.: 0 AF XY: 0.000981 AC XY: 4 AN XY: 4078

African (AFR) AF: 0.00909 AC: 1 AN: 110

American (AMR) AF: 0.00181 AC: 2 AN: 1106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 64

East Asian (EAS) AF: 0.00 AC: 0 AN: 202

South Asian (SAS) AF: 0.00 AC: 0 AN: 1764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 122

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.000294 AC: 1 AN: 3400

Other (OTH) AF: 0.00368 AC: 1 AN: 272

GnomAD4 genome AF: 0.0125 AC: 1901 AN: 152320 Hom.: 46 Cov.: 32 AF XY: 0.0119 AC XY: 883 AN XY: 74486

African (AFR) AF: 0.0437 AC: 1818 AN: 41566

American (AMR) AF: 0.00327 AC: 50 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0136

Asia WGS AF: 0.00346 AC: 13 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.65
PhyloP100		0.16
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs11811211; hg19: chr1-40723422;