chr6-30057726-G-A

Variant names:

• chr6-30057726-G-A
• rs259919
• ENST00000420251.5:n.437+389C>T

Variant summary

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

The ENST00000420251.5(POLR1HASP):​n.437+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 197,588 control chromosomes in the GnomAD database, including 7,464 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 0.26 (5517 hom., cov: 32)
  • Exomes 𝑓: 0.28 (1947 hom.)
• Consequence: POLR1HASP ENST00000420251.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 53 publications found

Genes affected

POLR1HASP (HGNC:):

POLR1HASP (HGNC:13924): (POLR1H antisense, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1HASP	NR_026751.2	n.442+389C>T		intron_variant	Intron 3 of 5
POLR1HASP	NR_145416.1	n.442+389C>T		intron_variant	Intron 3 of 6
POLR1HASP	NR_145417.1	n.442-9C>T		intron_variant	Intron 2 of 2
POLR1HASP	NR_145418.1	n.188-9C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1HASP	ENST00000420251.5	n.437+389C>T		intron_variant	Intron 3 of 5	1
POLR1HASP	ENST00000431012.5	n.178-9C>T		intron_variant	Intron 2 of 2	1
POLR1HASP	ENST00000437417.5	n.976+389C>T		intron_variant	Intron 2 of 5	1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38823 AN: 151916 Hom.: 5507 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.279 AC: 12701 AN: 45554 Hom.: 1947 Cov.: 0 AF XY: 0.280 AC XY: 6920 AN XY: 24692

African (AFR) AF: 0.137 AC: 95 AN: 694

American (AMR) AF: 0.208 AC: 675 AN: 3250

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 189 AN: 810

East Asian (EAS) AF: 0.256 AC: 543 AN: 2120

South Asian (SAS) AF: 0.261 AC: 1918 AN: 7346

European-Finnish (FIN) AF: 0.329 AC: 713 AN: 2168

Middle Eastern (MID) AF: 0.280 AC: 42 AN: 150

European-Non Finnish (NFE) AF: 0.295 AC: 7917 AN: 26836

Other (OTH) AF: 0.279 AC: 609 AN: 2180

GnomAD4 genome AF: 0.256 AC: 38845 AN: 152034 Hom.: 5517 Cov.: 32 AF XY: 0.257 AC XY: 19092 AN XY: 74304

African (AFR) AF: 0.127 AC: 5259 AN: 41508

American (AMR) AF: 0.235 AC: 3594 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1533 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10542

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21654 AN: 67946

Other (OTH) AF: 0.232 AC: 489 AN: 2106

Alfa AF: 0.299 Hom.: 30995

Bravo AF: 0.241

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.67
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs259919; hg19: chr6-30025503;