chr6-31973780-G-A

Variant names:

• chr6-31973780-G-A
• rs387608
• NM_004197.2:c.237+1023G>A

Variant summary

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

The NM_004197.2(WHR1):​c.237+1023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,010 control chromosomes in the GnomAD database, including 3,579 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 (3579 hom., cov: 32)
• Consequence: WHR1 NM_004197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 50 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WHR1	NM_004197.2	MANE Select	c.237+1023G>A		intron	N/A	NP_004188.2
	WHR1	NM_032454.1		c.567+1023G>A		intron	N/A	NP_115830.1	P49842-1
	WHR1	NR_026717.1		n.880+1023G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WHR1	ENST00000685781.1	MANE Select	c.237+1023G>A		intron	N/A	ENSP00000509445.1	P49842-4
	WHR1	ENST00000375333.4	TSL:1	c.567+1023G>A		intron	N/A	ENSP00000364482.4	P49842-1
	WHR1	ENST00000375331.8	TSL:1	c.567+1023G>A		intron	N/A	ENSP00000364480.4	P49842-2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29120 AN: 151892 Hom.: 3571 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29162 AN: 152010 Hom.: 3579 Cov.: 32 AF XY: 0.190 AC XY: 14096 AN XY: 74306

African (AFR) AF: 0.342 AC: 14181 AN: 41414

American (AMR) AF: 0.192 AC: 2935 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3468

East Asian (EAS) AF: 0.153 AC: 794 AN: 5184

South Asian (SAS) AF: 0.203 AC: 977 AN: 4810

European-Finnish (FIN) AF: 0.0670 AC: 708 AN: 10562

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8662 AN: 67980

Other (OTH) AF: 0.212 AC: 447 AN: 2108

Alfa AF: 0.144 Hom.: 8530

Bravo AF: 0.208

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.75
PhyloP100		0.0
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: rs387608; hg19: chr6-31941557;