rs1800778

Variant names:

• chr5-138465324-C-T
• rs1800778
• NM_001964.3:c.-438C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001964.3(EGR1):​c.-438C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,224 control chromosomes in the GnomAD database, including 59 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 0.022 (59 hom., cov: 33)
• Consequence: EGR1 NM_001964.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0224 (3411/152224) while in subpopulation NFE AF= 0.0317 (2155/67962). AF 95% confidence interval is 0.0306. There are 59 homozygotes in gnomad4. There are 1680 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3411 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR1	NM_001964.3	c.-438C>T		upstream_gene_variant		ENST00000239938.5	NP_001955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR1	ENST00000239938.5	c.-438C>T		upstream_gene_variant		1	NM_001964.3	ENSP00000239938.4

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3411 AN: 152108 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0224 AC: 3411 AN: 152224 Hom.: 59 Cov.: 33 AF XY: 0.0226 AC XY: 1680 AN XY: 74422

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0313 Hom.: 15

Bravo AF: 0.0184

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.0
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800778; hg19: chr5-137801013;