NM_001945.3:c.273C>T

Variant names:

• chr5-140342760-G-A
• rs2074611
• NM_001945.3:c.273C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001945.3(HBEGF):​c.273C>T​(p.His91His) 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001945.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBEGF	NM_001945.3	MANE Select	c.273C>T	p.His91His	synonymous	Exon 3 of 6	NP_001936.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBEGF	ENST00000230990.7	TSL:1 MANE Select	c.273C>T	p.His91His	synonymous	Exon 3 of 6	ENSP00000230990.6
	HBEGF	ENST00000950444.1		c.273C>T	p.His91His	synonymous	Exon 3 of 5	ENSP00000620503.1
	HBEGF	ENST00000950442.1		c.273C>T	p.His91His	synonymous	Exon 3 of 6	ENSP00000620501.1

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

GnomAD2 exomes AF: 0.0917 AC: 23064 AN: 251468 AF XY: 0.0905

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 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

African (AFR) AF: 0.188 AC: 6290 AN: 33480

American (AMR) AF: 0.0618 AC: 2762 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3525 AN: 26132

East Asian (EAS) AF: 0.113 AC: 4471 AN: 39700

South Asian (SAS) AF: 0.102 AC: 8838 AN: 86254

European-Finnish (FIN) AF: 0.115 AC: 6140 AN: 53416

Middle Eastern (MID) AF: 0.101 AC: 584 AN: 5768

European-Non Finnish (NFE) AF: 0.0730 AC: 81198 AN: 1111920

Other (OTH) AF: 0.0891 AC: 5379 AN: 60394

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

African (AFR) AF: 0.186 AC: 7714 AN: 41450

American (AMR) AF: 0.0842 AC: 1288 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3470

East Asian (EAS) AF: 0.105 AC: 544 AN: 5178

South Asian (SAS) AF: 0.119 AC: 572 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10590

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0743 AC: 5055 AN: 68008

Other (OTH) AF: 0.108 AC: 229 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.81
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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