rs971696

chr4-110006709-A-T

Variant summary

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

The NM_001963.6(EGF):c.3292-1443A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,146 control chromosomes in the GnomAD database, including 10,635 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 0.27 (10635 hom., cov: 33)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGF	NM_001963.6	c.3292-1443A>T		intron_variant		ENST00000265171.10
EGF	NM_001178130.3	c.3169-1443A>T		intron_variant
EGF	NM_001178131.3	c.3166-1443A>T		intron_variant
EGF	NM_001357021.2	c.2922+2087A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGF	ENST00000265171.10	c.3292-1443A>T		intron_variant		1	NM_001963.6	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40900 AN: 152028 Hom.: 10569 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.0860

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.270 AC: 41034 AN: 152146 Hom.: 10635 Cov.: 33 AF XY: 0.272 AC XY: 20254 AN XY: 74378

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.0860

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.224

Alfa AF: 0.183 Hom.: 755

Bravo AF: 0.305

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.5
Dann	Benign	0.41

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: rs971696; hg19: chr4-110927865;