rs2237076

Positions:

• chr5-140341246-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.398+1389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,130 control chromosomes in the GnomAD database, including 7,710 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 0.31 (7710 hom., cov: 32)
• Consequence: HBEGF NM_001945.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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]

HBEGF (HGNC:):

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 = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBEGF	NM_001945.3	c.398+1389G>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.398+1389G>A		intron_variant		1	NM_001945.3	ENSP00000230990.6
HBEGF	ENST00000498452.1	n.428+1389G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46862 AN: 152012 Hom.: 7706 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.308 AC: 46897 AN: 152130 Hom.: 7710 Cov.: 32 AF XY: 0.309 AC XY: 22990 AN XY: 74368

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.299

Alfa AF: 0.289 Hom.: 1077

Bravo AF: 0.310

Asia WGS AF: 0.225 AC: 781 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	1.7
DANN	Benign	0.46

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: rs2237076; hg19: chr5-139720831;