rs2074611

Positions:

• chr5-140342760-G-A
• chr5-140342760-G-C
• chr5-140342760-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001945.3(HBEGF):​c.273C>T​(p.His91=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,613,916 control chromosomes in the GnomAD database, including 6,550 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 0.11 (1150 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5400 hom.)
• Consequence: HBEGF NM_001945.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

Genes affected

HBEGF (HGNC:3059): (heparin binding EGF like growth factor) Enables growth factor activity and heparin binding activity. Involved in several processes, including epidermal growth factor receptor signaling pathway; positive regulation of protein kinase B signaling; and positive regulation of wound healing. Located in cell surface and extracellular space. Implicated in glomerulosclerosis and perinatal necrotizing enterocolitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.026 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBEGF	NM_001945.3	c.273C>T	p.His91=	synonymous_variant	3/6	ENST00000230990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBEGF	ENST00000230990.7	c.273C>T	p.His91=	synonymous_variant	3/6	1	NM_001945.3	P1
HBEGF	ENST00000498452.1	n.303C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17163 AN: 152010 Hom.: 1151 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0917 AC: 23064 AN: 251468 Hom.: 1277 AF XY: 0.0905 AC XY: 12293 AN XY: 135904

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.0607

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0724

Gnomad OTH exome AF: 0.0922

GnomAD4 exome AF: 0.0815 AC: 119187 AN: 1461788 Hom.: 5400 Cov.: 31 AF XY: 0.0819 AC XY: 59567 AN XY: 727200

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0730

Gnomad4 OTH exome AF: 0.0891

GnomAD4 genome AF: 0.113 AC: 17170 AN: 152128 Hom.: 1150 Cov.: 32 AF XY: 0.114 AC XY: 8491 AN XY: 74370

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0927 Hom.: 401

Bravo AF: 0.114

Asia WGS AF: 0.135 AC: 467 AN: 3478

EpiCase AF: 0.0726

EpiControl AF: 0.0722

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.81

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: rs2074611; hg19: chr5-139722345; COSMIC: COSV50182264;