chr4-109912994-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001963.6(EGF):​c.-342C>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 0.00668 in 303,384 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

EGF
NM_001963.6 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0270
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 Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 4-109912994-C-T is Benign according to our data. Variant chr4-109912994-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317925.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1821/152312) while in subpopulation AFR AF= 0.0413 (1715/41562). AF 95% confidence interval is 0.0396. There are 29 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGFNM_001963.6 linkuse as main transcriptc.-342C>T 5_prime_UTR_variant 1/24 ENST00000265171.10
EGFNM_001178130.3 linkuse as main transcriptc.-342C>T 5_prime_UTR_variant 1/23
EGFNM_001178131.3 linkuse as main transcriptc.-342C>T 5_prime_UTR_variant 1/23
EGFNM_001357021.2 linkuse as main transcriptc.-342C>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.-342C>T 5_prime_UTR_variant 1/241 NM_001963.6 P1P01133-1
EGFENST00000509793.5 linkuse as main transcriptc.-342C>T 5_prime_UTR_variant 1/232 P01133-2
EGFENST00000652245.1 linkuse as main transcriptc.-342C>T 5_prime_UTR_variant 1/20

Frequencies

GnomAD3 genomes
AF:
0.0119
AC:
1808
AN:
152194
Hom.:
29
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0411
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00543
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00765
GnomAD4 exome
AF:
0.00137
AC:
207
AN:
151072
Hom.:
5
Cov.:
0
AF XY:
0.00111
AC XY:
89
AN XY:
80476
show subpopulations
Gnomad4 AFR exome
AF:
0.0378
Gnomad4 AMR exome
AF:
0.00275
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000202
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000113
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
AF:
0.0120
AC:
1821
AN:
152312
Hom.:
29
Cov.:
32
AF XY:
0.0112
AC XY:
835
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0413
Gnomad4 AMR
AF:
0.00542
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00201
Hom.:
6
Bravo
AF:
0.0136

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 14, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
12
DANN
Benign
0.79

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: rs11568847; hg19: chr4-110834150; API