rs11568995

Positions:

• chr4-109976429-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001963.6(EGF):​c.2053+194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,202 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.027 (76 hom., cov: 32)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.875

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 4-109976429-G-A is Benign according to our data. Variant chr4-109976429-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.027 (4111/152202) while in subpopulation AFR AF= 0.045 (1869/41534). AF 95% confidence interval is 0.0433. There are 76 homozygotes in gnomad4. There are 2000 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGF	NM_001963.6	c.2053+194G>A		intron_variant		ENST00000265171.10
EGF	NM_001178130.3	c.2053+194G>A		intron_variant
EGF	NM_001178131.3	c.1927+194G>A		intron_variant
EGF	NM_001357021.2	c.1927+194G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGF	ENST00000265171.10	c.2053+194G>A		intron_variant		1	NM_001963.6	P1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4107 AN: 152084 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0270 AC: 4111 AN: 152202 Hom.: 76 Cov.: 32 AF XY: 0.0269 AC XY: 2000 AN XY: 74416

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0330

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0251 Hom.: 8

Bravo AF: 0.0269

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.67
DANN	Benign	0.77

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: rs11568995; hg19: chr4-110897585;