dbSNP rs34548063: WHR1:p.Trp17* (chr6-31972046-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_032454.1(WHR1):c.50G>A(p.Trp17*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,611,794 control chromosomes in the GnomAD database, including 41 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 0.0095 ( 27 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 14 hom. )

Consequence

WHR1
NM_032454.1 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.829

Publications

6 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:

DXO (HGNC:2992): (decapping exoribonuclease) This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene. [provided by RefSeq, Jul 2008]

DXO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00952 (1451/152390) while in subpopulation AFR AF = 0.033 (1371/41594). AF 95% confidence interval is 0.0315. There are 27 homozygotes in GnomAd4. There are 705 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032454.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DXO	NM_005510.4	MANE Select	c.-124C>T		5_prime_UTR	Exon 1 of 7	NP_005501.2
WHR1	NM_032454.1		c.50G>A	p.Trp17*	stop_gained	Exon 1 of 8	NP_115830.1	P49842-1
DXO	NM_001438478.1		c.-371C>T		5_prime_UTR	Exon 1 of 6	NP_001425407.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WHR1	ENST00000375333.4	TSL:1	c.50G>A	p.Trp17*	stop_gained	Exon 1 of 8	ENSP00000364482.4	P49842-1
WHR1	ENST00000375331.8	TSL:1	c.50G>A	p.Trp17*	stop_gained	Exon 1 of 8	ENSP00000364480.4	P49842-2
DXO	ENST00000337523.10	TSL:1 MANE Select	c.-124C>T		5_prime_UTR	Exon 1 of 7	ENSP00000337759.5	O77932

Frequencies

GnomAD3 genomes

AF:

0.00950

AC:

1447

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00241

AC:

597

AN:

247822

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000815

AC:

1190

AN:

1459404

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

515

AN XY:

725536

show subpopulations

African (AFR)

AF:

0.0273

AC:

914

AN:

33438

American (AMR)

AF:

0.00186

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.000162

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1110472

Other (OTH)

AF:

0.00206

AC:

124

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

162

242

323

404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00952

AC:

1451

AN:

152390

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

705

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.0330

AC:

1371

AN:

41594

American (AMR)

AF:

0.00411

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00347

Hom.:

Bravo

AF:

0.0107

ESP6500AA

AF:

0.0329

AC:

145

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00297

AC:

360

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.0048

PhyloP100

0.83

Vest4

0.049

GERP RS

-1.1

PromoterAI

0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=164/36

disease causing (fs/PTC)

(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