rs2074613

Positions:

• chr5-140334979-C-T

Variant summary

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

The NM_001945.3(HBEGF):​c.555-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 583,366 control chromosomes in the GnomAD database, including 91,959 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 0.60 (27672 hom., cov: 32)
  • Exomes 𝑓: 0.54 (64287 hom.)
• Consequence: HBEGF NM_001945.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBEGF	NM_001945.3	c.555-231G>A		intron_variant		ENST00000230990.7	NP_001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBEGF	ENST00000230990.7	c.555-231G>A		intron_variant		1	NM_001945.3	ENSP00000230990	P1
HBEGF	ENST00000482211.2	n.152G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90544 AN: 151906 Hom.: 27653 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.543 AC: 234327 AN: 431340 Hom.: 64287 Cov.: 0 AF XY: 0.541 AC XY: 123096 AN XY: 227538

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.553

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.596 AC: 90598 AN: 152026 Hom.: 27672 Cov.: 32 AF XY: 0.591 AC XY: 43956 AN XY: 74318

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.582

Alfa AF: 0.570 Hom.: 4667

Bravo AF: 0.610

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.75

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: rs2074613; hg19: chr5-139714564; COSMIC: COSV50182300; COSMIC: COSV50182300;