4-109952770-T-C

Variant summary

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

The NM_001963.6(EGF):c.941-6542T>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 152,050 control chromosomes in the GnomAD database, including 25,374 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 0.55 (25374 hom., cov: 32)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGF	NM_001963.6	c.941-6542T>C		intron_variant		ENST00000265171.10
EGF	NM_001178130.3	c.941-6542T>C		intron_variant
EGF	NM_001178131.3	c.940+7495T>C		intron_variant
EGF	NM_001357021.2	c.940+7495T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGF	ENST00000265171.10	c.941-6542T>C		intron_variant		1	NM_001963.6	P1
EGF	ENST00000503392.1	c.941-6542T>C		intron_variant		1
EGF	ENST00000509793.5	c.940+7495T>C		intron_variant		2
EGF	ENST00000652245.1	c.940+7495T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82752 AN: 151934 Hom.: 25305 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.401

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: 82879 AN: 152050 Hom.: 25374 Cov.: 32 AF XY: 0.543 AC XY: 40346 AN XY: 74340

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.535

Alfa AF: 0.452 Hom.: 8460

Bravo AF: 0.575

Asia WGS AF: 0.608 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.55

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: rs3796944; hg19: chr4-110873926;