Genetic Variant NM_001965.4:c.*52C>T (chr2-73291405-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001965.4(EGR4):c.*52C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,527,060 control chromosomes in the GnomAD database, including 15,401 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3886 hom., cov: 33)

Exomes 𝑓: 0.094 ( 11515 hom. )

Consequence

EGR4
NM_001965.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.623

Publications

10 publications found

Variant links:

Genes affected

EGR4 (HGNC:3241): (early growth response 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

EGR4 links:

ENSG00000310032 (HGNC:):

ENSG00000310032 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR4	NM_001965.4 link	c.*52C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000436467.4	NP_001956.4	Q05215B7ZKU3
EGR4	XM_047443603.1 link	c.*52C>T		3_prime_UTR_variant	Exon 2 of 2		XP_047299559.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EGR4	ENST00000436467.4 link	c.*52C>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_001965.4	ENSP00000419687.1	A0A0C4DG96
EGR4	ENST00000545030.1 link	c.*52C>T	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000445626.1	Q05215
ENSG00000310032	ENST00000846694.1 link	n.174-7161G>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26737

AN:

152098

Hom.:

3873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.0626

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.0554

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.0944

AC:

129848

AN:

1374842

Hom.:

11515

Cov.:

AF XY:

0.0963

AC XY:

64975

AN XY:

674382

show subpopulations

African (AFR)

AF:

0.378

AC:

11565

AN:

30568

American (AMR)

AF:

0.218

AC:

7008

AN:

32086

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

2758

AN:

20734

East Asian (EAS)

AF:

0.441

AC:

17112

AN:

38782

South Asian (SAS)

AF:

0.217

AC:

15582

AN:

71646

European-Finnish (FIN)

AF:

0.0547

AC:

2674

AN:

48914

Middle Eastern (MID)

AF:

0.145

AC:

632

AN:

4360

European-Non Finnish (NFE)

AF:

0.0612

AC:

65542

AN:

1071264

Other (OTH)

AF:

0.123

AC:

6975

AN:

56488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

5465

10931

16396

21862

27327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3074

6148

9222

12296

15370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26789

AN:

152218

Hom.:

3886

Cov.:

AF XY:

0.178

AC XY:

13223

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.365

AC:

15169

AN:

41512

American (AMR)

AF:

0.184

AC:

2819

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3472

East Asian (EAS)

AF:

0.423

AC:

2176

AN:

5140

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4820

European-Finnish (FIN)

AF:

0.0554

AC:

589

AN:

10628

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0601

AC:

4090

AN:

68024

Other (OTH)

AF:

0.166

AC:

350

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

990

1980

2970

3960

4950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

404

Bravo

AF:

0.198

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.83

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over