NM_170783.4:c.356+79T>A

Variant names:

• chr6-30062412-T-A
• rs9261271
• NM_170783.4:c.356+79T>A

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+79T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 973,520 control chromosomes in the GnomAD database, including 1,612 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 0.052 (255 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1357 hom.)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0644 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.356+79T>A		intron	N/A	NP_740753.1	Q9P1U0
	POLR1H	NM_001278785.2		c.356+79T>A		intron	N/A	NP_001265714.1	Q9P1U0
	POLR1H	NM_001278786.2		c.356+79T>A		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.356+79T>A		intron	N/A	ENSP00000331111.5	Q9P1U0
	POLR1H	ENST00000359374.8	TSL:1	c.356+79T>A		intron	N/A	ENSP00000352333.4	Q9P1U0
	POLR1H	ENST00000471008.5	TSL:1	n.3435+79T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7902 AN: 152166 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0501 AC: 41140 AN: 821236 Hom.: 1357 AF XY: 0.0497 AC XY: 21147 AN XY: 425664

African (AFR) AF: 0.0451 AC: 940 AN: 20856

American (AMR) AF: 0.0496 AC: 1809 AN: 36438

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 3404 AN: 21250

East Asian (EAS) AF: 0.0799 AC: 2699 AN: 33774

South Asian (SAS) AF: 0.0240 AC: 1665 AN: 69408

European-Finnish (FIN) AF: 0.0242 AC: 1089 AN: 45012

Middle Eastern (MID) AF: 0.0413 AC: 188 AN: 4556

European-Non Finnish (NFE) AF: 0.0493 AC: 27139 AN: 550868

Other (OTH) AF: 0.0565 AC: 2207 AN: 39074

GnomAD4 genome AF: 0.0520 AC: 7916 AN: 152284 Hom.: 255 Cov.: 32 AF XY: 0.0518 AC XY: 3854 AN XY: 74468

African (AFR) AF: 0.0496 AC: 2062 AN: 41546

American (AMR) AF: 0.0678 AC: 1037 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.0364 AC: 189 AN: 5190

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4832

European-Finnish (FIN) AF: 0.0236 AC: 250 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3505 AN: 68014

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0570 Hom.: 37

Bravo AF: 0.0545

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		-0.13
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: rs9261271; hg19: chr6-30030189;