Variant 5-54981998-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007036.5(ESM1):c.450G>A(p.Thr150=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,780 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 144 hom. )

Consequence

ESM1
NM_007036.5 splice_region, synonymous

Scores

Splicing: ADA: 0.00003282

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

Variant links:

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]

ESM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 5-54981998-C-T is Benign according to our data. Variant chr5-54981998-C-T is described in ClinVar as [Benign]. Clinvar id is 773932.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESM1	NM_007036.5 linkuse as main transcript	c.450G>A	p.Thr150=	splice_region_variant, synonymous_variant	2/3	ENST00000381405.5
ESM1	NM_001135604.2 linkuse as main transcript	c.302-2563G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESM1	ENST00000381405.5 linkuse as main transcript	c.450G>A	p.Thr150=	splice_region_variant, synonymous_variant	2/3	1	NM_007036.5	P1	Q9NQ30-1
ESM1	ENST00000381403.4 linkuse as main transcript	c.302-2563G>A		intron_variant		1			Q9NQ30-2
ESM1	ENST00000598310.5 linkuse as main transcript	n.230-2563G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1272

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00936

AC:

2352

AN:

251224

Hom.:

AF XY:

0.00988

AC XY:

1342

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00873

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0117

AC:

17159

AN:

1461510

Hom.:

144

Cov.:

AF XY:

0.0116

AC XY:

8463

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00939

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.00960

GnomAD4 genome

AF:

0.00835

AC:

1272

AN:

152270

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

637

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00781

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over