rs544759335

Variant names:

• chr4-109913434-C-A
• NM_001963.6:c.99C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-109913434-C-A
• chr4-109913434-C-G
• chr4-109913434-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001963.6(EGF):​c.99C>A​(p.Leu33Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EGF NM_001963.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.75 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGF	NM_001963.6	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 24	ENST00000265171.10	NP_001954.2
EGF	NM_001178130.3	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 23		NP_001171601.1
EGF	NM_001178131.3	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 23		NP_001171602.1
EGF	NM_001357021.2	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 20		NP_001343950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGF	ENST00000265171.10	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 24	1	NM_001963.6	ENSP00000265171.5
EGF	ENST00000503392.1	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 23	1		ENSP00000421384.1
EGF	ENST00000509793.5	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 23	2		ENSP00000424316.1
EGF	ENST00000652245.1	c.99C>A	p.Leu33Leu	synonymous_variant	Exon 1 of 20			ENSP00000498337.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-110834590;