rs1860129

chr4-109965187-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001963.6(EGF):c.1575+650G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,924 control chromosomes in the GnomAD database, including 25,315 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 0.54 (25315 hom., cov: 32)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGF	NM_001963.6	c.1575+650G>C		intron_variant		ENST00000265171.10
EGF	NM_001178130.3	c.1575+650G>C		intron_variant
EGF	NM_001178131.3	c.1449+650G>C		intron_variant
EGF	NM_001357021.2	c.1449+650G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGF	ENST00000265171.10	c.1575+650G>C		intron_variant		1	NM_001963.6	P1
EGF	ENST00000503392.1	c.1575+650G>C		intron_variant		1
EGF	ENST00000509793.5	c.1449+650G>C		intron_variant		2
EGF	ENST00000652245.1	c.1449+650G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82600 AN: 151806 Hom.: 25247 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.545 AC: 82727 AN: 151924 Hom.: 25315 Cov.: 32 AF XY: 0.542 AC XY: 40259 AN XY: 74244

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.536

Alfa AF: 0.492 Hom.: 2579

Bravo AF: 0.575

Asia WGS AF: 0.604 AC: 2099 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	12
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs1860129; hg19: chr4-110886343;