rs13385

Positions:

• chr5-140333293-G-A
• chr5-140333293-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001945.3(HBEGF):​c.*1006C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 154,056 control chromosomes in the GnomAD database, including 3,323 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 0.19 (3253 hom., cov: 32)
  • Exomes 𝑓: 0.25 (70 hom.)
• Consequence: HBEGF NM_001945.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBEGF	NM_001945.3	c.*1006C>T		3_prime_UTR_variant	6/6	ENST00000230990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBEGF	ENST00000230990.7	c.*1006C>T		3_prime_UTR_variant	6/6	1	NM_001945.3	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28570 AN: 152094 Hom.: 3239 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.251 AC: 462 AN: 1842 Hom.: 70 Cov.: 0 AF XY: 0.248 AC XY: 248 AN XY: 998

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.359

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.188 AC: 28608 AN: 152214 Hom.: 3253 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74410

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.188

Alfa AF: 0.216 Hom.: 7586

Bravo AF: 0.174

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.76

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: rs13385; hg19: chr5-139712878; COSMIC: COSV50182480; COSMIC: COSV50182480;