rs3757327

Positions:

• chr6-30059636-G-A
• chr6-30059636-G-C

Variant summary

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

The ENST00000471008.5(POLR1H):​n.738G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,106 control chromosomes in the GnomAD database, including 2,252 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 0.15 (2252 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: POLR1H ENST00000471008.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

Genes affected

POLR1H (HGNC:13182): (RNA polymerase I subunit H) This gene encodes a DNA-directed RNA polymerase I subunit. The encoded protein contains two potential zinc-binding motifs and may play a role in regulation of cell proliferation. The encoded protein may be involved in cancer and human immunodeficiency virus progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1HASP	NR_026751.2	n.366+1105C>T		intron_variant, non_coding_transcript_variant
POLR1HASP	NR_145416.1	n.366+1105C>T		intron_variant, non_coding_transcript_variant
POLR1HASP	NR_145418.1	n.111+1443C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1HASP	ENST00000688495.1	n.284+1105C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22547 AN: 151988 Hom.: 2240 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.173

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.149 AC: 22592 AN: 152106 Hom.: 2252 Cov.: 32 AF XY: 0.146 AC XY: 10888 AN XY: 74358

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.173

Alfa AF: 0.112 Hom.: 733

Bravo AF: 0.164

Asia WGS AF: 0.181 AC: 631 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
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: rs3757327; hg19: chr6-30027413;