6-30062337-A-G

Variant names:

• chr6-30062337-A-G
• rs9261269
• NM_170783.4:c.356+4A>G

Variant summary

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

The NM_170783.4(POLR1H):​c.356+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,596,914 control chromosomes in the GnomAD database, including 626,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61562 hom., cov: 31)
  • Exomes 𝑓: 0.88 (564541 hom.)
• Consequence: POLR1H NM_170783.4 splice_region, intron
• Scores: Splicing: ADA: 0.3109
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 19 publications found

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:):

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.356+4A>G		splice_region_variant, intron_variant	Intron 3 of 3	ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.356+4A>G		splice_region_variant, intron_variant	Intron 3 of 3	1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136642 AN: 152094 Hom.: 61499 Cov.: 31

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.893

GnomAD2 exomes AF: 0.904 AC: 223273 AN: 247020 AF XY: 0.904

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.991

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.874

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.883 AC: 1276274 AN: 1444702 Hom.: 564541 Cov.: 28 AF XY: 0.885 AC XY: 637150 AN XY: 719782

African (AFR) AF: 0.920 AC: 30530 AN: 33194

American (AMR) AF: 0.933 AC: 41720 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 23546 AN: 26000

East Asian (EAS) AF: 0.993 AC: 39331 AN: 39626

South Asian (SAS) AF: 0.937 AC: 80554 AN: 85990

European-Finnish (FIN) AF: 0.877 AC: 45880 AN: 52288

Middle Eastern (MID) AF: 0.894 AC: 5126 AN: 5734

European-Non Finnish (NFE) AF: 0.872 AC: 956372 AN: 1097340

Other (OTH) AF: 0.889 AC: 53215 AN: 59834

GnomAD4 genome AF: 0.899 AC: 136764 AN: 152212 Hom.: 61562 Cov.: 31 AF XY: 0.899 AC XY: 66941 AN XY: 74424

African (AFR) AF: 0.919 AC: 38162 AN: 41514

American (AMR) AF: 0.917 AC: 14023 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5106 AN: 5174

South Asian (SAS) AF: 0.945 AC: 4560 AN: 4824

European-Finnish (FIN) AF: 0.889 AC: 9427 AN: 10600

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59320 AN: 68012

Other (OTH) AF: 0.894 AC: 1889 AN: 2112

Alfa AF: 0.885 Hom.: 158581

Bravo AF: 0.903

Asia WGS AF: 0.960 AC: 3340 AN: 3478

EpiCase AF: 0.883

EpiControl AF: 0.884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.6
DANN	Benign	0.47
PhyloP100		-0.026
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.31
dbscSNV1_RF	Benign	0.36
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9261269; hg19: chr6-30030114;