rs3820152

Variant names:

• chr1-202909364-T-A
• rs3820152
• NM_021633.4:c.718-240A>T

Variant summary

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

The NM_021633.4(KLHL12):​c.718-240A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 150,688 control chromosomes in the GnomAD database, including 23,590 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 0.55 (23590 hom., cov: 30)
• Consequence: KLHL12 NM_021633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 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.718-240A>T		intron	N/A	NP_067646.1
	KLHL12	NM_001303051.2		c.832-240A>T		intron	N/A	NP_001289980.1
	KLHL12	NM_001303109.2		c.718-240A>T		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.718-240A>T		intron	N/A	ENSP00000356230.3
	KLHL12	ENST00000367258.1	TSL:5	c.832-240A>T		intron	N/A	ENSP00000356227.1
	KLHL12	ENST00000367259.1	TSL:2	c.-324A>T		upstream_gene	N/A	ENSP00000356228.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 82966 AN: 150570 Hom.: 23588 Cov.: 30

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.551 AC: 82998 AN: 150688 Hom.: 23590 Cov.: 30 AF XY: 0.551 AC XY: 40498 AN XY: 73536

African (AFR) AF: 0.436 AC: 17782 AN: 40776

American (AMR) AF: 0.565 AC: 8516 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2003 AN: 3462

East Asian (EAS) AF: 0.333 AC: 1693 AN: 5088

South Asian (SAS) AF: 0.419 AC: 1983 AN: 4734

European-Finnish (FIN) AF: 0.672 AC: 7027 AN: 10454

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42122 AN: 67800

Other (OTH) AF: 0.581 AC: 1218 AN: 2096

Alfa AF: 0.592 Hom.: 3362

Bravo AF: 0.540

Asia WGS AF: 0.375 AC: 1304 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	2.4
DANN	Benign	0.79
PhyloP100		0.37
PromoterAI		-0.017	Neutral
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: rs3820152; hg19: chr1-202878492;