Genetic Variant RFX8:c.562-113A>G (chr2-101413184-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.369

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RFX8	NM_001145664.2 link	c.562-113A>G		intron_variant	Intron 7 of 11	ENST00000428343.6	NP_001139136.2	Q6ZV50-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RFX8	ENST00000428343.6 link	c.562-113A>G	intron_variant	Intron 7 of 11	2	NM_001145664.2	ENSP00000401536.1	Q6ZV50-3
RFX8	ENST00000646893.2 link	c.901-113A>G	intron_variant	Intron 10 of 14			ENSP00000494249.2	Q6ZV50-1A0A2R8YED2
RFX8	ENST00000646446.1 link	c.775-113A>G	intron_variant	Intron 10 of 14			ENSP00000494216.1	A0A2R8Y560
RFX8	ENST00000481179.5 link	n.*278-113A>G	intron_variant	Intron 9 of 13	2		ENSP00000422968.1	E9PDA6

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23005

AN:

152126

Hom.:

1917

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.217

AC:

3322

AN:

15280

American (AMR)

AF:

0.110

AC:

2468

AN:

22444

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

3015

AN:

18926

East Asian (EAS)

AF:

0.0892

AC:

2867

AN:

32152

South Asian (SAS)

AF:

0.161

AC:

9234

AN:

57386

European-Finnish (FIN)

AF:

0.0662

AC:

2374

AN:

35838

Middle Eastern (MID)

AF:

0.170

AC:

581

AN:

3410

European-Non Finnish (NFE)

AF:

0.134

AC:

53148

AN:

397520

Other (OTH)

AF:

0.146

AC:

4706

AN:

32186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3584

7167

10751

14334

17918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.151

AC:

23015

AN:

152244

Hom.:

1918

Cov.:

AF XY:

0.147

AC XY:

10975

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.221

AC:

9180

AN:

41546

American (AMR)

AF:

0.129

AC:

1967

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

573

AN:

3468

East Asian (EAS)

AF:

0.0825

AC:

427

AN:

5176

South Asian (SAS)

AF:

0.164

AC:

789

AN:

4824

European-Finnish (FIN)

AF:

0.0522

AC:

555

AN:

10622

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9104

AN:

68004

Other (OTH)

AF:

0.156

AC:

329

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1011

2022

3033

4044

5055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.137

Hom.:

1855

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

(source)

DANN

Benign

0.49

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over