Menu
GeneBe

5-138466962-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001964.3(EGR1):c.513G>C(p.Ser171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,892 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 44 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 31 hom. )

Consequence

EGR1
NM_001964.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63
Variant links:
Genes affected
EGR1 (HGNC:3238): (early growth response 1) The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppressor gene. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-138466962-G-C is Benign according to our data. Variant chr5-138466962-G-C is described in ClinVar as [Benign]. Clinvar id is 768032.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.63 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2016/152072) while in subpopulation AFR AF= 0.0462 (1915/41440). AF 95% confidence interval is 0.0445. There are 44 homozygotes in gnomad4. There are 951 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 2011 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGR1NM_001964.3 linkuse as main transcriptc.513G>C p.Ser171= synonymous_variant 2/2 ENST00000239938.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGR1ENST00000239938.5 linkuse as main transcriptc.513G>C p.Ser171= synonymous_variant 2/21 NM_001964.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0132
AC:
2011
AN:
151954
Hom.:
44
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0462
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00387
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00361
AC:
908
AN:
251344
Hom.:
12
AF XY:
0.00273
AC XY:
371
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.0483
Gnomad AMR exome
AF:
0.00281
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00137
AC:
2000
AN:
1461820
Hom.:
31
Cov.:
33
AF XY:
0.00119
AC XY:
867
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0465
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000989
Gnomad4 OTH exome
AF:
0.00298
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0133
AC:
2016
AN:
152072
Hom.:
44
Cov.:
32
AF XY:
0.0128
AC XY:
951
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0462
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00110
Hom.:
1
Bravo
AF:
0.0157
Asia WGS
AF:
0.00260
AC:
10
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 submitterclinical testingInvitaeAug 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.94
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs11953917; hg19: chr5-137802651; COSMIC: COSV53522181; API