rs7692976

Variant names:

• chr4-109990411-A-G
• rs7692976
• NM_001963.6:c.2734+1702A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-109990411-A-G
• chr4-109990411-A-T

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+1702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,082 control chromosomes in the GnomAD database, including 25,440 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 0.55 (25440 hom., cov: 32)
• Consequence: EGF NM_001963.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGF	NM_001963.6	c.2734+1702A>G		intron_variant	Intron 18 of 23	ENST00000265171.10	NP_001954.2
EGF	NM_001178130.3	c.2734+1702A>G		intron_variant	Intron 18 of 22		NP_001171601.1
EGF	NM_001178131.3	c.2608+1702A>G		intron_variant	Intron 17 of 22		NP_001171602.1
EGF	NM_001357021.2	c.2366-2836A>G		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+1702A>G		intron_variant	Intron 18 of 23	1	NM_001963.6	ENSP00000265171.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83384 AN: 151964 Hom.: 25368 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.549 AC: 83522 AN: 152082 Hom.: 25440 Cov.: 32 AF XY: 0.549 AC XY: 40824 AN XY: 74338

African (AFR) AF: 0.817 AC: 33927 AN: 41512

American (AMR) AF: 0.533 AC: 8141 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3466

East Asian (EAS) AF: 0.695 AC: 3596 AN: 5174

South Asian (SAS) AF: 0.518 AC: 2496 AN: 4814

European-Finnish (FIN) AF: 0.399 AC: 4208 AN: 10552

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27956 AN: 67972

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.504 Hom.: 2783

Bravo AF: 0.572

Asia WGS AF: 0.621 AC: 2160 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	0.52
DANN	Benign	0.39
PhyloP100		-0.23
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: rs7692976; hg19: chr4-110911567;