rs2194205

Positions:

• chr5-55009883-G-C

Variant summary

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

The ENST00000601836.1(ESM1):​c.-444+12745C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,010 control chromosomes in the GnomAD database, including 37,557 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 0.69 (37557 hom., cov: 32)
• Consequence: ESM1 ENST00000601836.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESM1	ENST00000601836.1	c.-444+12745C>G		intron_variant		5
ESM1	ENST00000598310.5	n.44+12745C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104522 AN: 151892 Hom.: 37502 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.688 AC: 104638 AN: 152010 Hom.: 37557 Cov.: 32 AF XY: 0.689 AC XY: 51165 AN XY: 74288

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.668

Alfa AF: 0.635 Hom.: 3988

Bravo AF: 0.710

Asia WGS AF: 0.684 AC: 2379 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2194205; hg19: chr5-54305711;