4-109983292-C-T

Position:

• chr4-109983292-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001963.6(EGF):​c.2372-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,087,190 control chromosomes in the GnomAD database, including 111,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (23705 hom., cov: 32)
  • Exomes 𝑓: 0.42 (88164 hom.)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-109983292-C-T is Benign according to our data. Variant chr4-109983292-C-T is described in ClinVar as [Benign]. Clinvar id is 1250332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGF	NM_001963.6	c.2372-130C>T		intron_variant		ENST00000265171.10	NP_001954.2
EGF	NM_001178130.3	c.2372-130C>T		intron_variant			NP_001171601.1
EGF	NM_001178131.3	c.2246-130C>T		intron_variant			NP_001171602.1
EGF	NM_001357021.2	c.2246-130C>T		intron_variant			NP_001343950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGF	ENST00000265171.10	c.2372-130C>T		intron_variant		1	NM_001963.6	ENSP00000265171	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79539 AN: 151942 Hom.: 23631 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.423 AC: 395838 AN: 935130 Hom.: 88164 AF XY: 0.423 AC XY: 202229 AN XY: 478304

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.524 AC: 79680 AN: 152060 Hom.: 23705 Cov.: 32 AF XY: 0.523 AC XY: 38884 AN XY: 74338

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.504

Alfa AF: 0.449 Hom.: 4139

Bravo AF: 0.554

Asia WGS AF: 0.589 AC: 2050 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.48

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: rs6824594; hg19: chr4-110904448;