rs6850557

Variant names:

• chr4-109989859-G-A
• rs6850557
• NM_001963.6:c.2734+1150G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-109989859-G-A
• chr4-109989859-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001963.6(EGF):​c.2734+1150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,878 control chromosomes in the GnomAD database, including 4,992 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 0.24 (4992 hom., cov: 32)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• familial primary hypomagnesemia with normocalciuria and normocalcemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypomagnesemia 4

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGF	NM_001963.6	c.2734+1150G>A		intron_variant	Intron 18 of 23	ENST00000265171.10	NP_001954.2
EGF	NM_001178130.3	c.2734+1150G>A		intron_variant	Intron 18 of 22		NP_001171601.1
EGF	NM_001178131.3	c.2608+1150G>A		intron_variant	Intron 17 of 22		NP_001171602.1
EGF	NM_001357021.2	c.2366-3388G>A		intron_variant	Intron 15 of 19		NP_001343950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGF	ENST00000265171.10	c.2734+1150G>A		intron_variant	Intron 18 of 23	1	NM_001963.6	ENSP00000265171.5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36567 AN: 151760 Hom.: 4992 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.241 AC: 36569 AN: 151878 Hom.: 4992 Cov.: 32 AF XY: 0.238 AC XY: 17680 AN XY: 74186

African (AFR) AF: 0.134 AC: 5547 AN: 41446

American (AMR) AF: 0.238 AC: 3637 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3470

East Asian (EAS) AF: 0.0815 AC: 421 AN: 5164

South Asian (SAS) AF: 0.233 AC: 1118 AN: 4798

European-Finnish (FIN) AF: 0.286 AC: 3005 AN: 10498

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20804 AN: 67930

Other (OTH) AF: 0.262 AC: 552 AN: 2108

Alfa AF: 0.212 Hom.: 2017

Bravo AF: 0.233

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.49
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6850557; hg19: chr4-110911015;