6-30061030-A-C

Variant names:

• chr6-30061030-A-C
• rs7769930
• ENST00000437417.5:n.611T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000437417.5(POLR1HASP):​n.611T>G 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 0.147 in 153,862 control chromosomes in the GnomAD database, including 2,242 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 (2235 hom., cov: 33)
  • Exomes 𝑓: 0.074 (7 hom.)
• Consequence: POLR1HASP ENST00000437417.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• Publications: 14 publications found

Genes affected

POLR1HASP (HGNC:):

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)

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437417.5. 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
	POLR1HASP	NR_026751.2		n.112-35T>G		intron	N/A
	POLR1HASP	NR_145416.1		n.112-35T>G		intron	N/A
	POLR1HASP	NR_145418.1		n.111+49T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1HASP	ENST00000437417.5	TSL:1	n.611T>G		non_coding_transcript_exon	Exon 1 of 6
	POLR1H	ENST00000471008.5	TSL:1	n.2132A>C		non_coding_transcript_exon	Exon 1 of 2
	POLR1HASP	ENST00000420251.5	TSL:1	n.107-35T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22505 AN: 152114 Hom.: 2225 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.0742 AC: 121 AN: 1630 Hom.: 7 Cov.: 0 AF XY: 0.0831 AC XY: 72 AN XY: 866

African (AFR) AF: 0.241 AC: 13 AN: 54

American (AMR) AF: 0.111 AC: 8 AN: 72

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 12 AN: 48

East Asian (EAS) AF: 0.118 AC: 4 AN: 34

South Asian (SAS) AF: 0.0924 AC: 22 AN: 238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.0540 AC: 59 AN: 1092

Other (OTH) AF: 0.0333 AC: 2 AN: 60

GnomAD4 genome AF: 0.148 AC: 22543 AN: 152232 Hom.: 2235 Cov.: 33 AF XY: 0.146 AC XY: 10883 AN XY: 74454

African (AFR) AF: 0.267 AC: 11078 AN: 41490

American (AMR) AF: 0.150 AC: 2295 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.154 AC: 798 AN: 5186

South Asian (SAS) AF: 0.160 AC: 773 AN: 4830

European-Finnish (FIN) AF: 0.0318 AC: 338 AN: 10624

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5857 AN: 68016

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.116 Hom.: 2533

Bravo AF: 0.164

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.46
PhyloP100		0.35
PromoterAI		-0.034	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7769930; hg19: chr6-30028807;