2-101416523-G-A

Variant names:

• chr2-101416523-G-A
• rs7564703
• NM_001145664.2:c.502+1011C>T

Variant summary

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

The NM_001145664.2(RFX8):​c.502+1011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,172 control chromosomes in the GnomAD database, including 66,761 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 0.93 (66761 hom., cov: 31)
• Consequence: RFX8 NM_001145664.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145664.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX8	NM_001145664.2	MANE Select	c.502+1011C>T		intron	N/A	NP_001139136.2
	RFX8	NM_001367508.1		c.48+1011C>T		intron	N/A	NP_001354437.1
	RFX8	NM_001367509.1		c.48+1011C>T		intron	N/A	NP_001354438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX8	ENST00000428343.6	TSL:2 MANE Select	c.502+1011C>T		intron	N/A	ENSP00000401536.1
	RFX8	ENST00000646893.2		c.841+1011C>T		intron	N/A	ENSP00000494249.2
	RFX8	ENST00000646446.1		c.715+1011C>T		intron	N/A	ENSP00000494216.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142061 AN: 152054 Hom.: 66735 Cov.: 31

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.934 AC: 142140 AN: 152172 Hom.: 66761 Cov.: 31 AF XY: 0.933 AC XY: 69408 AN XY: 74428

African (AFR) AF: 0.842 AC: 34940 AN: 41474

American (AMR) AF: 0.885 AC: 13518 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 0.864 AC: 4457 AN: 5158

South Asian (SAS) AF: 0.988 AC: 4771 AN: 4828

European-Finnish (FIN) AF: 0.973 AC: 10326 AN: 10612

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67508 AN: 68032

Other (OTH) AF: 0.938 AC: 1982 AN: 2114

Alfa AF: 0.968 Hom.: 193428

Bravo AF: 0.920

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.46
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7564703; hg19: chr2-102032985;