Genetic Variant WHR1:c.473+130G>C (chr6-31979683-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004197.2(WHR1):c.473+130G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000088 in 1,136,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)

Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

WHR1
NM_004197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
WHR1	NM_004197.2 link	c.473+130G>C	intron_variant	Intron 4 of 6	ENST00000685781.1	NP_004188.2	P49842-4A0A1U9X8L3
WHR1	NM_032454.1 link	c.815+130G>C	intron_variant	Intron 5 of 7		NP_115830.1	P49842-1
WHR1	NR_026717.1 link	n.1116+130G>C	intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK19	ENST00000685781.1 link	c.473+130G>C		intron_variant	Intron 4 of 6		NM_004197.2	ENSP00000509445.1		P49842-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.80e-7

AC:

AN:

1136358

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

562974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26222

American (AMR)

AF:

0.00

AC:

AN:

26622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18410

East Asian (EAS)

AF:

0.00

AC:

AN:

37526

South Asian (SAS)

AF:

0.00

AC:

AN:

63444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3494

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

875790

Other (OTH)

AF:

0.00

AC:

AN:

48628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

(source)

DANN

Benign

0.70

PhyloP100

-0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over