2-101420168-G-C

Position:

• chr2-101420168-G-C

Variant summary

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

The NM_001145664.2(RFX8):​c.238-1204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,150 control chromosomes in the GnomAD database, including 64,526 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 0.92 (64526 hom., cov: 30)
• Consequence: RFX8 NM_001145664.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 (SAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX8	NM_001145664.2	c.238-1204C>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.238-1204C>G		intron_variant		2	NM_001145664.2	ENSP00000401536
RFX8	ENST00000646446.1	c.451-1204C>G		intron_variant				ENSP00000494216
RFX8	ENST00000646893.2	c.577-1204C>G		intron_variant				ENSP00000494249	P1
RFX8	ENST00000481179.5	c.*13-1204C>G		intron_variant, NMD_transcript_variant		2		ENSP00000422968

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139636 AN: 152034 Hom.: 64493 Cov.: 30

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.918 AC: 139722 AN: 152150 Hom.: 64526 Cov.: 30 AF XY: 0.917 AC XY: 68249 AN XY: 74394

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.915

Alfa AF: 0.942 Hom.: 8419

Bravo AF: 0.900

Asia WGS AF: 0.918 AC: 3193 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	2.9
DANN	Benign	0.67

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: rs7591334; hg19: chr2-102036630;