5-54981998-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007036.5(ESM1):​c.450G>A​(p.Thr150Thr) 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

2
Splicing: ADA: 0.00003282
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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_multiple_submitters_no_conflicts, 2 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 rank MANE Protein UniProt
ESM1NM_007036.5 linkc.450G>A p.Thr150Thr splice_region_variant, synonymous_variant Exon 2 of 3 ENST00000381405.5 NP_008967.1 Q9NQ30-1
ESM1NM_001135604.2 linkc.302-2563G>A intron_variant Intron 1 of 1 NP_001129076.1 Q9NQ30-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESM1ENST00000381405.5 linkc.450G>A p.Thr150Thr splice_region_variant, synonymous_variant Exon 2 of 3 1 NM_007036.5 ENSP00000370812.4 Q9NQ30-1
ESM1ENST00000381403.4 linkc.302-2563G>A intron_variant Intron 1 of 1 1 ENSP00000370810.4 Q9NQ30-2
ESM1ENST00000598310.5 linkn.230-2563G>A intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.00836
AC:
1272
AN:
152152
Hom.:
10
Cov.:
32
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.:
18
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.:
30
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.:
10
Cov.:
32
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.:
16
Bravo
AF:
0.00781
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.0112
EpiControl
AF:
0.0135

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 19, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
12
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.

Other links and lift over

dbSNP: rs142604597; hg19: chr5-54277826; API