Genetic Variant WHR1:c.473+130G>T (chr6-31979683-G-T) – 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.473+130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,285,820 control chromosomes in the GnomAD database, including 344,962 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 0.80 ( 48871 hom., cov: 29)

Exomes 𝑓: 0.72 ( 296091 hom. )

Consequence

WHR1
NM_004197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990

Publications

86 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WHR1	NM_004197.2	MANE Select	c.473+130G>T	intron	N/A	NP_004188.2
WHR1	NM_032454.1		c.815+130G>T	intron	N/A	NP_115830.1	P49842-1
WHR1	NR_026717.1		n.1116+130G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WHR1	ENST00000685781.1	MANE Select	c.473+130G>T	intron	N/A	ENSP00000509445.1	P49842-4
WHR1	ENST00000375333.4	TSL:1	c.815+130G>T	intron	N/A	ENSP00000364482.4	P49842-1
WHR1	ENST00000375331.8	TSL:1	c.803+130G>T	intron	N/A	ENSP00000364480.4	P49842-2

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120793

AN:

151920

Hom.:

48804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.833

GnomAD4 exome

AF:

0.717

AC:

813373

AN:

1133782

Hom.:

296091

Cov.:

AF XY:

0.723

AC XY:

406094

AN XY:

561734

show subpopulations

African (AFR)

AF:

0.926

AC:

24267

AN:

26210

American (AMR)

AF:

0.847

AC:

22503

AN:

26578

Ashkenazi Jewish (ASJ)

AF:

0.866

AC:

15924

AN:

18390

East Asian (EAS)

AF:

0.690

AC:

25837

AN:

37470

South Asian (SAS)

AF:

0.894

AC:

56691

AN:

63380

European-Finnish (FIN)

AF:

0.725

AC:

26230

AN:

36156

Middle Eastern (MID)

AF:

0.888

AC:

3096

AN:

3488

European-Non Finnish (NFE)

AF:

0.690

AC:

602903

AN:

873584

Other (OTH)

AF:

0.740

AC:

35922

AN:

48526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10324

20648

30971

41295

51619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15058

30116

45174

60232

75290

<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:

0.795

AC:

120920

AN:

152038

Hom.:

48871

Cov.:

AF XY:

0.800

AC XY:

59411

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.920

AC:

38130

AN:

41456

American (AMR)

AF:

0.848

AC:

12963

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3030

AN:

3470

East Asian (EAS)

AF:

0.685

AC:

3544

AN:

5176

South Asian (SAS)

AF:

0.888

AC:

4268

AN:

4806

European-Finnish (FIN)

AF:

0.745

AC:

7877

AN:

10568

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48315

AN:

67962

Other (OTH)

AF:

0.834

AC:

1757

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1170

2339

3509

4678

5848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.742

Hom.:

171723

Bravo

AF:

0.808

Asia WGS

AF:

0.850

AC:

2958

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.6

(source)

DANN

Benign

0.76

PhyloP100

-0.099

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