1-202902110-T-C

Variant names:

• chr1-202902110-T-C
• rs7542125
• NM_021633.4:c.833-5150A>G

Variant summary

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

The NM_021633.4(KLHL12):​c.833-5150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,116 control chromosomes in the GnomAD database, including 4,685 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 0.23 (4685 hom., cov: 32)
• Consequence: KLHL12 NM_021633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929
• Publications: 6 publications found

Genes affected

KLHL12 (HGNC:19360): (kelch like family member 12) This gene encodes a member of the KLHL (Kelch-like) family of proteins. This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis. This protein may act as a substrate adaptor of the Cullin-3 ubiquitin ligase complex to promote substrate-specific ubiquitylation. Ubiquitylation by this complex has been shown to regulate the Wnt signaling pathway as well as COPII vesicle coat size. A pseudogene has been identified on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021633.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL12	NM_021633.4	MANE Select	c.833-5150A>G		intron	N/A	NP_067646.1
	KLHL12	NM_001303051.2		c.947-5150A>G		intron	N/A	NP_001289980.1
	KLHL12	NM_001303109.2		c.832+6900A>G		intron	N/A	NP_001290038.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL12	ENST00000367261.8	TSL:1 MANE Select	c.833-5150A>G		intron	N/A	ENSP00000356230.3
	KLHL12	ENST00000367259.1	TSL:2	c.32-5150A>G		intron	N/A	ENSP00000356228.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35104 AN: 151998 Hom.: 4665 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.231 AC: 35156 AN: 152116 Hom.: 4685 Cov.: 32 AF XY: 0.237 AC XY: 17656 AN XY: 74346

African (AFR) AF: 0.147 AC: 6099 AN: 41504

American (AMR) AF: 0.274 AC: 4176 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.568 AC: 2947 AN: 5184

South Asian (SAS) AF: 0.393 AC: 1897 AN: 4826

European-Finnish (FIN) AF: 0.272 AC: 2877 AN: 10560

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15759 AN: 67996

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.236 Hom.: 2333

Bravo AF: 0.222

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.93
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: rs7542125; hg19: chr1-202871238; COSMIC: COSV66127163;