4-109913276-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001963.6(EGF):​c.-60C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,606,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

EGF
NM_001963.6 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -2.03
Variant links:
Genes affected
EGF (HGNC:3229): (epidermal growth factor) This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGFNM_001963.6 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/24 ENST00000265171.10
EGFNM_001178130.3 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/23
EGFNM_001178131.3 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/23
EGFNM_001357021.2 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGFENST00000265171.10 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/241 NM_001963.6 P1P01133-1
EGFENST00000503392.1 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/231 P01133-3
EGFENST00000509793.5 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/232 P01133-2
EGFENST00000652245.1 linkuse as main transcriptc.-60C>T 5_prime_UTR_variant 1/20

Frequencies

GnomAD3 genomes
AF:
0.000966
AC:
147
AN:
152184
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00184
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00141
AC:
2048
AN:
1454212
Hom.:
0
Cov.:
30
AF XY:
0.00136
AC XY:
981
AN XY:
723552
show subpopulations
Gnomad4 AFR exome
AF:
0.000271
Gnomad4 AMR exome
AF:
0.000202
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000350
Gnomad4 FIN exome
AF:
0.0000765
Gnomad4 NFE exome
AF:
0.00177
Gnomad4 OTH exome
AF:
0.000951
GnomAD4 genome
AF:
0.000965
AC:
147
AN:
152302
Hom.:
1
Cov.:
33
AF XY:
0.000685
AC XY:
51
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00184
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00138
Hom.:
0
Bravo
AF:
0.000956

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Renal hypomagnesemia 4 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
6.0
DANN
Benign
0.62

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: rs191144589; hg19: chr4-110834432; API