Variant 2-101417555-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001145664.2(RFX8):c.481T>G(p.Leu161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,549,428 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 31 hom. )

Consequence

RFX8
NM_001145664.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68

Variant links:

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]

RFX8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070569515).

BP6

Variant 2-101417555-A-C is Benign according to our data. Variant chr2-101417555-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 771127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX8	NM_001145664.2 linkuse as main transcript	c.481T>G	p.Leu161Val	missense_variant	6/12	ENST00000428343.6	NP_001139136.2	Q6ZV50-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX8	ENST00000428343.6 linkuse as main transcript	c.481T>G	p.Leu161Val	missense_variant	6/12	2	NM_001145664.2	ENSP00000401536.1		Q6ZV50-3

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

513

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00507

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00326

AC:

506

AN:

155362

Hom.:

AF XY:

0.00346

AC XY:

284

AN XY:

82006

show subpopulations

Gnomad AFR exome

AF:

0.000490

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00231

Gnomad FIN exome

AF:

0.000177

Gnomad NFE exome

AF:

0.00552

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00498

AC:

6962

AN:

1397106

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

3374

AN XY:

689002

show subpopulations

Gnomad4 AFR exome

AF:

0.000764

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00590

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.000384

Gnomad4 NFE exome

AF:

0.00576

Gnomad4 OTH exome

AF:

0.00446

GnomAD4 genome

AF:

0.00335

AC:

510

AN:

152322

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00507

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00509

Hom.:

Bravo

AF:

0.00378

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00503

AC:

ExAC

AF:

0.00332

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.82

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0071

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

.;.;N

REVEL

Benign

0.024

Sift

Benign

0.17

.;.;T

Sift4G

Benign

0.10

.;.;T

Polyphen

0.015

.;.;B

Vest4

0.17

MVP

0.11

MPC

.;.;5.34477657668E-4

ClinPred

0.0030

GERP RS

3.2

gMVP

0.092

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over