rs61734275

chr7-19698375-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001002926.2(POLR1F):c.958G>A(p.Glu320Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,587,614 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: POLR1F NM_001002926.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96

Genes affected

POLR1F (HGNC:18027): (RNA polymerase I subunit F) Predicted to enable DNA-directed 5'-3' RNA polymerase activity. Predicted to be involved in DNA-templated transcription, initiation. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in nucleoplasm. Predicted to be part of RNA polymerase I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033777356).
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1F	NM_001002926.2	c.958G>A	p.Glu320Lys	missense_variant	4/4	ENST00000222567.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1F	ENST00000222567.6	c.958G>A	p.Glu320Lys	missense_variant	4/4	1	NM_001002926.2	P1

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 272 AN: 151982 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000568 AC: 128 AN: 225470 Hom.: 1 AF XY: 0.000482 AC XY: 59 AN XY: 122320

Gnomad AFR exome AF: 0.00684

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000606

Gnomad SAS exome AF: 0.000120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.000375

GnomAD4 exome AF: 0.000193 AC: 277 AN: 1435514 Hom.: 0 Cov.: 31 AF XY: 0.000156 AC XY: 111 AN XY: 713750

Gnomad4 AFR exome AF: 0.00583

Gnomad4 AMR exome AF: 0.000467

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000998

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000425

Gnomad4 OTH exome AF: 0.000372

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152100 Hom.: 2 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74346

Gnomad4 AFR AF: 0.00633

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000463 Hom.: 0

Bravo AF: 0.00207

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000642 AC: 78

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.089
Sift	Uncertain	0.025	D
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.091
MVP		0.48
MPC		0.51
ClinPred		0.051	T
GERP RS		5.5
Varity_R		0.062
gMVP		0.073

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: rs61734275; hg19: chr7-19737998; COSMIC: COSV99748577; COSMIC: COSV99748577;