Variant 2-101418897-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145664.2(RFX8):c.305C>T(p.Pro102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,551,620 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

RFX8
NM_001145664.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.33

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055042207).

BP6

Variant 2-101418897-G-A is Benign according to our data. Variant chr2-101418897-G-A is described in ClinVar as [Benign]. Clinvar id is 787238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1056/152292) while in subpopulation AFR AF= 0.0237 (986/41548). AF 95% confidence interval is 0.0225. There are 9 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX8	NM_001145664.2 linkuse as main transcript	c.305C>T	p.Pro102Leu	missense_variant	5/12	ENST00000428343.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX8	ENST00000428343.6 linkuse as main transcript	c.305C>T	p.Pro102Leu	missense_variant	5/12	2	NM_001145664.2		Q6ZV50-3
RFX8	ENST00000646893.2 linkuse as main transcript	c.644C>T	p.Pro215Leu	missense_variant	8/15			P1	Q6ZV50-1
RFX8	ENST00000646446.1 linkuse as main transcript	c.518C>T	p.Pro173Leu	missense_variant	8/15
RFX8	ENST00000481179.5 linkuse as main transcript	c.*80C>T		3_prime_UTR_variant, NMD_transcript_variant	8/14	2

Frequencies

GnomAD3 genomes

AF:

0.00694

AC:

1056

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00159

AC:

250

AN:

157394

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

83212

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.000730

AC:

1022

AN:

1399328

Hom.:

Cov.:

AF XY:

0.000613

AC XY:

423

AN XY:

690174

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000185

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00693

AC:

1056

AN:

152292

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00854

ESP6500AA

AF:

0.0275

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00232

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.0

.;.;D

REVEL

Benign

0.19

Sift

Uncertain

0.0030

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

0.21

.;.;B

Vest4

0.52

MVP

0.21

MPC

.;.;5.55450975E-4

ClinPred

0.092

GERP RS

3.9

gMVP

0.22

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