rs10493090

Variant names:

• chr1-40161246-G-T
• rs10493090
• ENST00000795129.1:n.12C>A

Variant summary

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

The ENST00000795129.1(ENSG00000303499):​n.12C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,025,584 control chromosomes in the GnomAD database, including 5,061 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 0.090 (705 hom., cov: 32)
  • Exomes 𝑓: 0.097 (4356 hom.)
• Consequence: ENSG00000303499 ENST00000795129.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 8 publications found

Genes affected

ENSG00000303499 (HGNC:):

RLF (HGNC:10025): (RLF zinc finger) Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within histone H3-K4 monomethylation and regulation of DNA methylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000795129.1. 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
	RLF	NM_012421.4	MANE Select	c.-154G>T		upstream_gene	N/A	NP_036553.2	Q13129

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000303499	ENST00000795129.1		n.12C>A		non_coding_transcript_exon	Exon 1 of 1
	RLF	ENST00000372771.5	TSL:1 MANE Select	c.-154G>T		upstream_gene	N/A	ENSP00000361857.4	Q13129

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13667 AN: 152150 Hom.: 703 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0842

GnomAD4 exome AF: 0.0971 AC: 84839 AN: 873316 Hom.: 4356 AF XY: 0.0975 AC XY: 42001 AN XY: 430626

African (AFR) AF: 0.0610 AC: 1095 AN: 17960

American (AMR) AF: 0.113 AC: 1306 AN: 11578

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 864 AN: 15294

East Asian (EAS) AF: 0.118 AC: 3230 AN: 27324

South Asian (SAS) AF: 0.142 AC: 6342 AN: 44506

European-Finnish (FIN) AF: 0.0902 AC: 2664 AN: 29522

Middle Eastern (MID) AF: 0.0621 AC: 176 AN: 2832

European-Non Finnish (NFE) AF: 0.0954 AC: 65331 AN: 685066

Other (OTH) AF: 0.0976 AC: 3831 AN: 39234

GnomAD4 genome AF: 0.0899 AC: 13689 AN: 152268 Hom.: 705 Cov.: 32 AF XY: 0.0918 AC XY: 6832 AN XY: 74442

African (AFR) AF: 0.0645 AC: 2681 AN: 41574

American (AMR) AF: 0.130 AC: 1990 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.151 AC: 782 AN: 5168

South Asian (SAS) AF: 0.153 AC: 740 AN: 4822

European-Finnish (FIN) AF: 0.0932 AC: 989 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6061 AN: 68012

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.0904 Hom.: 1276

Bravo AF: 0.0915

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.8
DANN	Benign	0.80
PhyloP100		-0.23
PromoterAI		0.082	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10493090; hg19: chr1-40626918;