5-138468946-T-C

Variant names:

• chr5-138468946-T-C
• rs6914
• NM_001964.3:c.*865T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001964.3(EGR1):​c.*865T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,334 control chromosomes in the GnomAD database, including 200 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 0.039 (199 hom., cov: 31)
  • Exomes 𝑓: 0.017 (1 hom.)
• Consequence: EGR1 NM_001964.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001964.3. 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
	EGR1	NM_001964.3	MANE Select	c.*865T>C		3_prime_UTR	Exon 2 of 2	NP_001955.1	P18146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR1	ENST00000239938.5	TSL:1 MANE Select	c.*865T>C		3_prime_UTR	Exon 2 of 2	ENSP00000239938.4	P18146

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5924 AN: 151806 Hom.: 199 Cov.: 31

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0198

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0171 AC: 7 AN: 410 Hom.: 1 Cov.: 0 AF XY: 0.0282 AC XY: 7 AN XY: 248

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0177 AC: 7 AN: 396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0390 AC: 5922 AN: 151924 Hom.: 199 Cov.: 31 AF XY: 0.0359 AC XY: 2664 AN XY: 74262

African (AFR) AF: 0.0117 AC: 483 AN: 41422

American (AMR) AF: 0.0422 AC: 643 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5162

South Asian (SAS) AF: 0.0196 AC: 94 AN: 4794

European-Finnish (FIN) AF: 0.0152 AC: 160 AN: 10554

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0624 AC: 4238 AN: 67958

Other (OTH) AF: 0.0342 AC: 72 AN: 2108

Alfa AF: 0.0532 Hom.: 90

Bravo AF: 0.0409

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		-0.011
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs6914; hg19: chr5-137804635;