ENST00000648240.1:c.-284C>T

Variant names:

• chr19-35106825-C-T
• rs7258700
• ENST00000648240.1:c.-284C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000648240.1(ENSG00000285526):​c.-284C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 455,222 control chromosomes in the GnomAD database, including 45,587 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 0.47 (17744 hom., cov: 32)
  • Exomes 𝑓: 0.43 (27843 hom.)
• Consequence: ENSG00000285526 ENST00000648240.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 5 publications found

Genes affected

ENSG00000285526 (HGNC:):

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.032).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648240.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285526	ENST00000648240.1		c.-284C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000497169.1
	ENSG00000285526	ENST00000648240.1		c.-284C>T		5_prime_UTR	Exon 1 of 9	ENSP00000497169.1
	ENSG00000179066	ENST00000313865.6	TSL:6	n.857C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71964 AN: 151880 Hom.: 17729 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.429 AC: 54970 AN: 128242 AF XY: 0.424

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.450

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.426 AC: 129043 AN: 303222 Hom.: 27843 Cov.: 0 AF XY: 0.421 AC XY: 72692 AN XY: 172616

African (AFR) AF: 0.603 AC: 5175 AN: 8578

American (AMR) AF: 0.428 AC: 11662 AN: 27258

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 4727 AN: 10766

East Asian (EAS) AF: 0.439 AC: 4042 AN: 9202

South Asian (SAS) AF: 0.399 AC: 23827 AN: 59726

European-Finnish (FIN) AF: 0.369 AC: 4561 AN: 12366

Middle Eastern (MID) AF: 0.419 AC: 1165 AN: 2780

European-Non Finnish (NFE) AF: 0.427 AC: 67646 AN: 158342

Other (OTH) AF: 0.439 AC: 6238 AN: 14204

GnomAD4 genome AF: 0.474 AC: 72014 AN: 152000 Hom.: 17744 Cov.: 32 AF XY: 0.470 AC XY: 34944 AN XY: 74286

African (AFR) AF: 0.607 AC: 25172 AN: 41446

American (AMR) AF: 0.451 AC: 6881 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.446 AC: 2301 AN: 5162

South Asian (SAS) AF: 0.401 AC: 1935 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3750 AN: 10536

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29128 AN: 67982

Other (OTH) AF: 0.451 AC: 953 AN: 2112

Alfa AF: 0.414 Hom.: 8193

Bravo AF: 0.483

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.72
PhyloP100		-0.99
PromoterAI		-0.073	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7258700; hg19: chr19-35597729; COSMIC: COSV58307281;