6-31979683-G-T

Variant names:

• chr6-31979683-G-T
• rs389883
• NM_004197.2:c.473+130G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 86 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120793 AN: 151920 Hom.: 48804 Cov.: 29

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.: 14 AF XY: 0.723 AC XY: 406094 AN XY: 561734

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

GnomAD4 genome AF: 0.795 AC: 120920 AN: 152038 Hom.: 48871 Cov.: 29 AF XY: 0.800 AC XY: 59411 AN XY: 74302

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs389883; hg19: chr6-31947460;