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:

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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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RFX8	NM_001145664.2	MANE Select	c.562-113A>G	intron	N/A	NP_001139136.2	Q6ZV50-3
RFX8	NM_001367508.1		c.49-113A>G	intron	N/A	NP_001354437.1
RFX8	NM_001367509.1		c.49-113A>G	intron	N/A	NP_001354438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RFX8	ENST00000428343.6	TSL:2 MANE Select	c.562-113A>G	intron	N/A	ENSP00000401536.1	Q6ZV50-3
RFX8	ENST00000646893.2		c.901-113A>G	intron	N/A	ENSP00000494249.2	Q6ZV50-1
RFX8	ENST00000646446.1		c.775-113A>G	intron	N/A	ENSP00000494216.1	A0A2R8Y560

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over