Genetic Variant WHR1:c.473+264G>C (chr6-31979817-G-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_004197.2(WHR1):c.473+264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 418,926 control chromosomes in the GnomAD database, including 6,910 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 0.19 ( 3604 hom., cov: 31)

Exomes 𝑓: 0.14 ( 3306 hom. )

Consequence

WHR1
NM_004197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

35 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 = 0.339 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+264G>C	intron	N/A	NP_004188.2
WHR1	NM_032454.1		c.815+264G>C	intron	N/A	NP_115830.1	P49842-1
WHR1	NR_026717.1		n.1116+264G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WHR1	ENST00000685781.1	MANE Select	c.473+264G>C	intron	N/A	ENSP00000509445.1	P49842-4
WHR1	ENST00000375333.4	TSL:1	c.815+264G>C	intron	N/A	ENSP00000364482.4	P49842-1
WHR1	ENST00000375331.8	TSL:1	c.803+264G>C	intron	N/A	ENSP00000364480.4	P49842-2

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29238

AN:

152028

Hom.:

3596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.143

AC:

38170

AN:

266778

Hom.:

3306

Cov.:

AF XY:

0.144

AC XY:

20044

AN XY:

138844

show subpopulations

African (AFR)

AF:

0.340

AC:

3086

AN:

9080

American (AMR)

AF:

0.164

AC:

2014

AN:

12310

Ashkenazi Jewish (ASJ)

AF:

0.0945

AC:

828

AN:

8764

East Asian (EAS)

AF:

0.173

AC:

3378

AN:

19492

South Asian (SAS)

AF:

0.209

AC:

4815

AN:

23016

European-Finnish (FIN)

AF:

0.0740

AC:

1095

AN:

14792

Middle Eastern (MID)

AF:

0.125

AC:

148

AN:

1188

European-Non Finnish (NFE)

AF:

0.125

AC:

20309

AN:

162162

Other (OTH)

AF:

0.156

AC:

2497

AN:

15974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1514

3028

4542

6056

7570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

222

444

666

888

1110

<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:

0.192

AC:

29279

AN:

152148

Hom.:

3604

Cov.:

AF XY:

0.190

AC XY:

14146

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.343

AC:

14242

AN:

41474

American (AMR)

AF:

0.193

AC:

2950

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

366

AN:

3472

East Asian (EAS)

AF:

0.154

AC:

797

AN:

5188

South Asian (SAS)

AF:

0.202

AC:

974

AN:

4816

European-Finnish (FIN)

AF:

0.0651

AC:

690

AN:

10602

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8717

AN:

67998

Other (OTH)

AF:

0.214

AC:

451

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1153

2307

3460

4614

5767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.106

Hom.:

595

Bravo

AF:

0.209

Asia WGS

AF:

0.245

AC:

854

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

3.3

(source)

DANN

Benign

0.42

PhyloP100

-0.028

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