chr6-30063568-T-C

Position:

• chr6-30063568-T-C

Variant summary

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

The NM_170783.4(POLR1H):​c.357-1105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,574 control chromosomes in the GnomAD database, including 13,270 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 0.42 (13270 hom., cov: 31)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

POLR1H (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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.357-1105T>C		intron_variant		ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.357-1105T>C		intron_variant		1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63257 AN: 151460 Hom.: 13238 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63332 AN: 151574 Hom.: 13270 Cov.: 31 AF XY: 0.419 AC XY: 31024 AN XY: 74046

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.428

Alfa AF: 0.422 Hom.: 23871

Bravo AF: 0.419

Asia WGS AF: 0.507 AC: 1760 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1150739; hg19: chr6-30031345;