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5-138467466-T-G

Variant summary

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

The NM_001964.3(EGR1):c.1017T>G(p.Ala339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,613,888 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 12 hom. )

Consequence

EGR1
NM_001964.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.340
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 -11 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=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-138467466-T-G is Benign according to our data. Variant chr5-138467466-T-G is described in ClinVar as [Benign]. Clinvar id is 773935.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=-0.34 with no splicing effect.
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 135 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGR1NM_001964.3 linkuse as main transcriptc.1017T>G p.Ala339= synonymous_variant 2/2 ENST00000239938.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGR1ENST00000239938.5 linkuse as main transcriptc.1017T>G p.Ala339= synonymous_variant 2/21 NM_001964.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000888
AC:
135
AN:
152056
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0102
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00154
AC:
388
AN:
251198
Hom.:
2
AF XY:
0.00188
AC XY:
255
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000983
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00885
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000554
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.000836
AC:
1222
AN:
1461712
Hom.:
12
Cov.:
33
AF XY:
0.00102
AC XY:
745
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000894
Gnomad4 ASJ exome
AF:
0.000536
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00846
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.000250
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000887
AC:
135
AN:
152176
Hom.:
1
Cov.:
32
AF XY:
0.00116
AC XY:
86
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0102
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000508
Hom.:
0
Bravo
AF:
0.000521
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000927
EpiControl
AF:
0.00107

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 testingInvitaeJun 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
7.8
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs141771089; hg19: chr5-137803155; API