chr6-29991969-A-G

Variant names:

• chr6-29991969-A-G
• rs9260952
• ENST00000422224.6:n.823-3742T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000422224.6(POLR1HASP):​n.823-3742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 143,038 control chromosomes in the GnomAD database, including 248 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 0.12 (248 hom., cov: 33)
• Consequence: POLR1HASP ENST00000422224.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 3 publications found

Genes affected

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High Homozygotes in GnomAd4 at 248 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1HASP	ENST00000422224.6	n.823-3742T>C		intron_variant	Intron 5 of 5	3
POLR1HASP	ENST00000688495.1	n.361-14574T>C		intron_variant	Intron 3 of 3
POLR1HASP	ENST00000849678.1	n.588+29698T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 16862 AN: 142920 Hom.: 247 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.118 AC: 16891 AN: 143038 Hom.: 248 Cov.: 33 AF XY: 0.117 AC XY: 8171 AN XY: 69986

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.180 AC: 6655 AN: 37066

American (AMR) AF: 0.146 AC: 2063 AN: 14110

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 822 AN: 3310

East Asian (EAS) AF: 0.129 AC: 619 AN: 4788

South Asian (SAS) AF: 0.109 AC: 482 AN: 4412

European-Finnish (FIN) AF: 0.0352 AC: 368 AN: 10442

Middle Eastern (MID) AF: 0.153 AC: 42 AN: 274

European-Non Finnish (NFE) AF: 0.0845 AC: 5557 AN: 65766

Other (OTH) AF: 0.134 AC: 263 AN: 1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0774 Hom.: 129

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs9260952; hg19: chr6-29959746;