rs1508891

Variant names:

• chr5-54986967-G-A
• rs1508891
• ENST00000601836.1:c.-443-1007C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-54986967-G-A
• chr5-54986967-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000601836.1(ESM1):​c.-443-1007C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 152,282 control chromosomes in the GnomAD database, including 27 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 0.012 (27 hom., cov: 32)
• Consequence: ESM1 ENST00000601836.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 1 publications found

Genes affected

ESM1 (HGNC:3466): (endothelial cell specific molecule 1) This gene encodes a secreted protein which is mainly expressed in the endothelial cells in human lung and kidney tissues. The expression of this gene is regulated by cytokines, suggesting that it may play a role in endothelium-dependent pathological disorders. The transcript contains multiple polyadenylation and mRNA instability signals. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1833/152282) while in subpopulation AFR AF = 0.0388 (1611/41546). AF 95% confidence interval is 0.0372. There are 27 homozygotes in GnomAd4. There are 904 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR 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
ESM1	ENST00000601836.1	c.-443-1007C>T		intron_variant	Intron 1 of 1	5		ENSP00000471642.1
ESM1	ENST00000598310.5	n.229+6580C>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1822 AN: 152164 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0120 AC: 1833 AN: 152282 Hom.: 27 Cov.: 32 AF XY: 0.0121 AC XY: 904 AN XY: 74460

African (AFR) AF: 0.0388 AC: 1611 AN: 41546

American (AMR) AF: 0.0100 AC: 153 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68026

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.00792 Hom.: 9

Bravo AF: 0.0142

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs1508891; hg19: chr5-54282795;