dbSNP rs389884: WHR1:c.237+363A>G (chr6-31973120-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004197.2(WHR1):c.237+363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 487,050 control chromosomes in the GnomAD database, including 1,926 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 0.069 ( 497 hom., cov: 32)

Exomes 𝑓: 0.070 ( 1429 hom. )

Consequence

WHR1
NM_004197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.23

Publications

80 publications found

Variant links:

Genes affected

WHR1 (HGNC:11398): (serine/threonine kinase 19) This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. [provided by RefSeq, Jul 2008]

WHR1 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=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WHR1	NM_004197.2 link	c.237+363A>G	intron_variant	Intron 2 of 6	ENST00000685781.1	NP_004188.2
WHR1	NM_032454.1 link	c.567+363A>G	intron_variant	Intron 3 of 7		NP_115830.1
WHR1	NR_026717.1 link	n.880+363A>G	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK19	ENST00000685781.1 link	c.237+363A>G		intron_variant	Intron 2 of 6		NM_004197.2	ENSP00000509445.1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10509

AN:

152110

Hom.:

497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0788

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0522

GnomAD4 exome

AF:

0.0704

AC:

23582

AN:

334822

Hom.:

1429

Cov.:

AF XY:

0.0653

AC XY:

11801

AN XY:

180814

show subpopulations

African (AFR)

AF:

0.0401

AC:

407

AN:

10152

American (AMR)

AF:

0.0241

AC:

552

AN:

22948

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

419

AN:

10370

East Asian (EAS)

AF:

0.000116

AC:

AN:

17254

South Asian (SAS)

AF:

0.000160

AC:

AN:

50120

European-Finnish (FIN)

AF:

0.0906

AC:

1548

AN:

17084

Middle Eastern (MID)

AF:

0.00644

AC:

AN:

2796

European-Non Finnish (NFE)

AF:

0.104

AC:

19312

AN:

186246

Other (OTH)

AF:

0.0737

AC:

1316

AN:

17852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1110

2220

3330

4440

5550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0690

AC:

10506

AN:

152228

Hom.:

497

Cov.:

AF XY:

0.0642

AC XY:

4780

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0394

AC:

1635

AN:

41544

American (AMR)

AF:

0.0320

AC:

489

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0386

AC:

134

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0788

AC:

835

AN:

10596

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7233

AN:

67996

Other (OTH)

AF:

0.0516

AC:

109

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

490

980

1469

1959

2449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0984

Hom.:

3845

Bravo

AF:

0.0646

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.7

(source)

DANN

Benign

0.88

PhyloP100

-3.2

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