rs1508890

chr5-54984179-C-A

Variant summary

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

The NM_007036.5(ESM1):c.301+1038G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,764 control chromosomes in the GnomAD database, including 6,967 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 0.19 (6967 hom., cov: 33)
• Consequence: ESM1 NM_007036.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESM1	NM_007036.5	c.301+1038G>T		intron_variant		ENST00000381405.5
ESM1	NM_001135604.2	c.301+1038G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESM1	ENST00000381405.5	c.301+1038G>T		intron_variant		1	NM_007036.5	P1
ESM1	ENST00000381403.4	c.301+1038G>T		intron_variant		1
ESM1	ENST00000598310.5	n.230-4744G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28859 AN: 151646 Hom.: 6938 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.191 AC: 28954 AN: 151764 Hom.: 6967 Cov.: 33 AF XY: 0.190 AC XY: 14091 AN XY: 74182

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00595

Gnomad4 OTH AF: 0.172

Alfa AF: 0.0945 Hom.: 734

Bravo AF: 0.224

Asia WGS AF: 0.287 AC: 981 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.95
Dann	Benign	0.25

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: rs1508890; hg19: chr5-54280007;