2-101413184-T-C

Position:

• chr2-101413184-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145664.2(RFX8):​c.562-113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 767,386 control chromosomes in the GnomAD database, including 7,837 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 0.15 (1918 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5919 hom.)
• Consequence: RFX8 NM_001145664.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

Genes affected

RFX8 (HGNC:37253): (regulatory factor X8) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX8	NM_001145664.2	c.562-113A>G		intron_variant		ENST00000428343.6	NP_001139136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX8	ENST00000428343.6	c.562-113A>G		intron_variant		2	NM_001145664.2	ENSP00000401536.1
RFX8	ENST00000646893.2	c.901-113A>G		intron_variant				ENSP00000494249.2
RFX8	ENST00000646446.1	c.775-113A>G		intron_variant				ENSP00000494216.1
RFX8	ENST00000481179.5	n.*278-113A>G		intron_variant		2		ENSP00000422968.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23005 AN: 152126 Hom.: 1917 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.133 AC: 81715 AN: 615142 Hom.: 5919 AF XY: 0.134 AC XY: 43820 AN XY: 326880

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.0662

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.151 AC: 23015 AN: 152244 Hom.: 1918 Cov.: 33 AF XY: 0.147 AC XY: 10975 AN XY: 74454

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.156

Alfa AF: 0.125 Hom.: 1048

Bravo AF: 0.159

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.49

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: rs12620464; hg19: chr2-102029646;