19-35106825-C-T

Variant names:

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

Variant summary

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

The ENST00000648240(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 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

Genes affected

ENSG00000285526 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904701	XM_047439795.1	c.*907C>T		3_prime_UTR_variant	Exon 2 of 2		XP_047295751.1
LOC124904701	XR_007067238.1	n.2500C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285526	ENST00000648240	c.-284C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9			ENSP00000497169.1
ENSG00000285526	ENST00000648240	c.-284C>T		5_prime_UTR_variant	Exon 1 of 9			ENSP00000497169.1

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

GnomAD3 exomes AF: 0.429 AC: 54970 AN: 128242 Hom.: 12001 AF XY: 0.424 AC XY: 29782 AN XY: 70234

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 SAS exome AF: 0.387

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

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.439

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

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.451

Alfa AF: 0.411 Hom.: 7431

Bravo AF: 0.483

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

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