chr6-30064542-G-C

Variant names:

• chr6-30064542-G-C
• rs11752321
• NM_170783.4:c.357-131G>C

Variant summary

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

The NM_170783.4(POLR1H):​c.357-131G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 685,642 control chromosomes in the GnomAD database, including 446 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 0.025 (118 hom., cov: 32)
  • Exomes 𝑓: 0.016 (328 hom.)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 4 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]

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]

POLR1HASP (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	NM_170783.4	MANE Select	c.357-131G>C		intron	N/A	NP_740753.1	Q9P1U0
	POLR1H	NM_001278785.2		c.357-131G>C		intron	N/A	NP_001265714.1	Q9P1U0
	POLR1H	NM_001278786.2		c.357-131G>C		intron	N/A	NP_001265715.1	Q9P1U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	ENST00000332435.10	TSL:1 MANE Select	c.357-131G>C		intron	N/A	ENSP00000331111.5	Q9P1U0
	POLR1H	ENST00000359374.8	TSL:1	c.357-131G>C		intron	N/A	ENSP00000352333.4	Q9P1U0
	POLR1H	ENST00000471008.5	TSL:1	n.3436-131G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3849 AN: 151928 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.000948

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00569

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0159 AC: 8468 AN: 533596 Hom.: 328 AF XY: 0.0178 AC XY: 4979 AN XY: 279256

African (AFR) AF: 0.0468 AC: 578 AN: 12338

American (AMR) AF: 0.00776 AC: 112 AN: 14424

Ashkenazi Jewish (ASJ) AF: 0.00483 AC: 64 AN: 13254

East Asian (EAS) AF: 0.0885 AC: 2531 AN: 28604

South Asian (SAS) AF: 0.0788 AC: 3011 AN: 38198

European-Finnish (FIN) AF: 0.00163 AC: 53 AN: 32548

Middle Eastern (MID) AF: 0.0251 AC: 51 AN: 2028

European-Non Finnish (NFE) AF: 0.00445 AC: 1624 AN: 364554

Other (OTH) AF: 0.0161 AC: 444 AN: 27648

GnomAD4 genome AF: 0.0254 AC: 3858 AN: 152046 Hom.: 118 Cov.: 32 AF XY: 0.0265 AC XY: 1971 AN XY: 74324

African (AFR) AF: 0.0529 AC: 2194 AN: 41464

American (AMR) AF: 0.0118 AC: 180 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.0887 AC: 459 AN: 5176

South Asian (SAS) AF: 0.113 AC: 544 AN: 4818

European-Finnish (FIN) AF: 0.000948 AC: 10 AN: 10544

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00569 AC: 387 AN: 67982

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0154 Hom.: 10

Bravo AF: 0.0261

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11752321; hg19: chr6-30032319;