5-140333293-G-A

Variant names:

• chr5-140333293-G-A
• rs13385
• NM_001945.3:c.*1006C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBEGF	NM_001945.3	MANE Select	c.*1006C>T		3_prime_UTR	Exon 6 of 6	NP_001936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBEGF	ENST00000230990.7	TSL:1 MANE Select	c.*1006C>T		3_prime_UTR	Exon 6 of 6	ENSP00000230990.6
	HBEGF	ENST00000482211.2	TSL:2	n.*231C>T		downstream_gene	N/A

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

African (AFR) AF: 0.250 AC: 4 AN: 16

American (AMR) AF: 0.333 AC: 8 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 6 AN: 40

East Asian (EAS) AF: 0.359 AC: 74 AN: 206

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.308 AC: 192 AN: 624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.196 AC: 166 AN: 848

Other (OTH) AF: 0.145 AC: 11 AN: 76

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

African (AFR) AF: 0.0662 AC: 2750 AN: 41564

American (AMR) AF: 0.205 AC: 3132 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1605 AN: 5182

South Asian (SAS) AF: 0.252 AC: 1214 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3074 AN: 10574

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15678 AN: 68000

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.209 Hom.: 11369

Bravo AF: 0.174

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		0.80
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: rs13385; hg19: chr5-139712878; COSMIC: COSV50182480; COSMIC: COSV50182480;