rs7514099

chr1-40261607-A-G

Variant summary

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

The NM_005857.5(ZMPSTE24):c.270+622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,094 control chromosomes in the GnomAD database, including 4,975 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 0.25 (4975 hom., cov: 32)
• Consequence: ZMPSTE24 NM_005857.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

ZMPSTE24 (HGNC:12877): (zinc metallopeptidase STE24) This gene encodes a member of the peptidase M48A family. The encoded protein is a zinc metalloproteinase involved in the two step post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A to form mature lamin A. Mutations in this gene have been associated with mandibuloacral dysplasia and restrictive dermopathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMPSTE24	NM_005857.5	c.270+622A>G		intron_variant		ENST00000372759.4
ZMPSTE24	XM_047427590.1	c.270+622A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMPSTE24	ENST00000372759.4	c.270+622A>G		intron_variant		1	NM_005857.5	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38352 AN: 151976 Hom.: 4975 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.252 AC: 38349 AN: 152094 Hom.: 4975 Cov.: 32 AF XY: 0.252 AC XY: 18700 AN XY: 74340

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.239

Alfa AF: 0.263 Hom.: 848

Bravo AF: 0.244

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.7
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7514099; hg19: chr1-40727279; COSMIC: COSV65638924; COSMIC: COSV65638924;