chr5-54981998-C-T

Variant names:

• chr5-54981998-C-T
• rs142604597
• NM_007036.5:c.450G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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: Splicing: ADA: 0.00003282
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53
• Publications: 3 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 -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007036.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESM1	NM_007036.5	MANE Select	c.450G>A	p.Thr150Thr	splice_region synonymous	Exon 2 of 3	NP_008967.1	Q9NQ30-1
	ESM1	NM_001135604.2		c.302-2563G>A		intron	N/A	NP_001129076.1	Q9NQ30-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESM1	ENST00000381405.5	TSL:1 MANE Select	c.450G>A	p.Thr150Thr	splice_region synonymous	Exon 2 of 3	ENSP00000370812.4	Q9NQ30-1
	ESM1	ENST00000381403.4	TSL:1	c.302-2563G>A		intron	N/A	ENSP00000370810.4	Q9NQ30-2
	ESM1	ENST00000598310.5	TSL:5	n.230-2563G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1272 AN: 152152 Hom.: 10 Cov.: 32

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

GnomAD2 exomes AF: 0.00936 AC: 2352 AN: 251224 AF XY: 0.00988

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 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

African (AFR) AF: 0.00209 AC: 70 AN: 33472

American (AMR) AF: 0.00458 AC: 205 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26118

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39696

South Asian (SAS) AF: 0.00939 AC: 810 AN: 86222

European-Finnish (FIN) AF: 0.0130 AC: 693 AN: 53410

Middle Eastern (MID) AF: 0.0123 AC: 71 AN: 5766

European-Non Finnish (NFE) AF: 0.0132 AC: 14696 AN: 1111720

Other (OTH) AF: 0.00960 AC: 580 AN: 60390

GnomAD4 genome AF: 0.00835 AC: 1272 AN: 152270 Hom.: 10 Cov.: 32 AF XY: 0.00856 AC XY: 637 AN XY: 74458

African (AFR) AF: 0.00217 AC: 90 AN: 41556

American (AMR) AF: 0.00569 AC: 87 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4822

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 872 AN: 68018

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.0103 Hom.: 21

Bravo AF: 0.00781

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0112

EpiControl AF: 0.0135

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.51
PhyloP100		1.5
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs142604597; hg19: chr5-54277826;