rs3869066

Variant names:

• chr6-30035987-A-G
• rs3869066
• ENST00000420251.5:n.438-4T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-30035987-A-G
• chr6-30035987-A-T

Variant summary

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

The ENST00000420251.5(POLR1HASP):​n.438-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 456,638 control chromosomes in the GnomAD database, including 376 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 0.022 (71 hom., cov: 32)
  • Exomes 𝑓: 0.031 (305 hom.)
• Consequence: POLR1HASP ENST00000420251.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

Genes affected

POLR1HASP (HGNC:13924): (POLR1H antisense, pseudogene)

ENSG00000278104 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1HASP	NR_026751.2	n.443-4T>C		splice_region_variant, intron_variant	Intron 3 of 5
POLR1HASP	NR_145416.1	n.443-4T>C		splice_region_variant, intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1HASP	ENST00000420251.5	n.438-4T>C		splice_region_variant, intron_variant	Intron 3 of 5	1
POLR1HASP	ENST00000437417.5	n.977-4T>C		splice_region_variant, intron_variant	Intron 2 of 5	1
POLR1HASP	ENST00000376797.7	n.260-4T>C		splice_region_variant, intron_variant	Intron 2 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3357 AN: 152224 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.0376 AC: 5144 AN: 136902 Hom.: 219 AF XY: 0.0344 AC XY: 2561 AN XY: 74350

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.0244

Gnomad SAS exome AF: 0.0271

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0320

GnomAD4 exome AF: 0.0310 AC: 9436 AN: 304296 Hom.: 305 Cov.: 0 AF XY: 0.0291 AC XY: 5048 AN XY: 173280

Gnomad4 AFR exome AF: 0.00556

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0219

Gnomad4 EAS exome AF: 0.0334

Gnomad4 SAS exome AF: 0.0276

Gnomad4 FIN exome AF: 0.0181

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0221 AC: 3365 AN: 152342 Hom.: 71 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74504

Gnomad4 AFR AF: 0.00717

Gnomad4 AMR AF: 0.0597

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.0316

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0282 Hom.: 45

Bravo AF: 0.0267

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3869066; hg19: chr6-30003764;