4-109970856-T-G

Position:

• chr4-109970856-T-G

Variant summary

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

The NM_001963.6(EGF):​c.1724+1737T>G 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 147,300 control chromosomes in the GnomAD database, including 24,633 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 (24633 hom., cov: 27)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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]

EGF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGF	NM_001963.6	c.1724+1737T>G		intron_variant		ENST00000265171.10	NP_001954.2
EGF	NM_001178130.3	c.1724+1737T>G		intron_variant			NP_001171601.1
EGF	NM_001178131.3	c.1598+1737T>G		intron_variant			NP_001171602.1
EGF	NM_001357021.2	c.1598+1737T>G		intron_variant			NP_001343950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGF	ENST00000265171.10	c.1724+1737T>G		intron_variant		1	NM_001963.6	ENSP00000265171.5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 80137 AN: 147204 Hom.: 24579 Cov.: 27

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.545 AC: 80240 AN: 147300 Hom.: 24633 Cov.: 27 AF XY: 0.543 AC XY: 38853 AN XY: 71496

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.530

Alfa AF: 0.453 Hom.: 9803

Bravo AF: 0.581

Asia WGS AF: 0.651 AC: 2266 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.30

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: rs2298991; hg19: chr4-110892012;