1-107056636-A-T

Variant names:

• chr1-107056636-A-T
• rs2232015
• ENST00000722404.1:n.869T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000722404.1(ENSG00000294279):​n.869T>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.321 in 1,440,018 control chromosomes in the GnomAD database, including 76,229 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 0.25 (5827 hom., cov: 33)
  • Exomes 𝑓: 0.33 (70402 hom.)
• Consequence: ENSG00000294279 ENST00000722404.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 16 publications found

Genes affected

ENSG00000294279 (HGNC:):

PRMT6 (HGNC:18241): (protein arginine methyltransferase 6) The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000722404.1. 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
	PRMT6	NM_018137.3	MANE Select	c.-80A>T		upstream_gene	N/A	NP_060607.2	Q96LA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000294279	ENST00000722404.1		n.869T>A		non_coding_transcript_exon	Exon 1 of 1
	PRMT6	ENST00000370078.2	TSL:6 MANE Select	c.-80A>T		upstream_gene	N/A	ENSP00000359095.1	Q96LA8-1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38666 AN: 152038 Hom.: 5822 Cov.: 33

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.329 AC: 423258 AN: 1287860 Hom.: 70402 Cov.: 26 AF XY: 0.330 AC XY: 206135 AN XY: 625398

African (AFR) AF: 0.0735 AC: 2055 AN: 27970

American (AMR) AF: 0.244 AC: 4781 AN: 19588

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 5033 AN: 18832

East Asian (EAS) AF: 0.284 AC: 9904 AN: 34856

South Asian (SAS) AF: 0.329 AC: 20555 AN: 62476

European-Finnish (FIN) AF: 0.292 AC: 12642 AN: 43226

Middle Eastern (MID) AF: 0.288 AC: 1037 AN: 3606

European-Non Finnish (NFE) AF: 0.342 AC: 350477 AN: 1024124

Other (OTH) AF: 0.315 AC: 16774 AN: 53182

GnomAD4 genome AF: 0.254 AC: 38678 AN: 152158 Hom.: 5827 Cov.: 33 AF XY: 0.253 AC XY: 18841 AN XY: 74406

African (AFR) AF: 0.0849 AC: 3529 AN: 41560

American (AMR) AF: 0.250 AC: 3829 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1547 AN: 5144

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4824

European-Finnish (FIN) AF: 0.292 AC: 3095 AN: 10592

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23240 AN: 67962

Other (OTH) AF: 0.248 AC: 523 AN: 2110

Alfa AF: 0.168 Hom.: 368

Bravo AF: 0.241

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		4.2
PromoterAI		-0.42	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2232015;

hg19: chr1-107599258;

COSMIC: COSV63656520;