rs7140768

Variant names:

• chr14-20428698-C-T
• rs7140768
• NM_001365790.2:c.*151G>A

Variant summary

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

The NM_001365790.2(KLHL33):​c.*151G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 717,230 control chromosomes in the GnomAD database, including 121,551 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 0.58 (25386 hom., cov: 33)
  • Exomes 𝑓: 0.58 (96165 hom.)
• Consequence: KLHL33 NM_001365790.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997
• Publications: 4 publications found

Genes affected

KLHL33 (HGNC:31952): (kelch like family member 33)

ENSG00000291038 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365790.2. 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
	KLHL33	NM_001365790.2	MANE Select	c.*151G>A		3_prime_UTR	Exon 5 of 5	NP_001352719.1	A0A1B0GUB7
	KLHL33	NM_001109997.3		c.*151G>A		3_prime_UTR	Exon 4 of 4	NP_001103467.2	A6NCF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	ENST00000636854.3	TSL:5 MANE Select	c.*151G>A		3_prime_UTR	Exon 5 of 5	ENSP00000490040.1	A0A1B0GUB7
	KLHL33	ENST00000637228.1	TSL:5	c.*704G>A		3_prime_UTR	Exon 4 of 4	ENSP00000489731.1	A0A1B0GTK0
	ENSG00000291038	ENST00000800199.1		n.212+1046C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87819 AN: 152036 Hom.: 25349 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.581 AC: 328073 AN: 565076 Hom.: 96165 Cov.: 7 AF XY: 0.585 AC XY: 169481 AN XY: 289864

African (AFR) AF: 0.569 AC: 8151 AN: 14322

American (AMR) AF: 0.504 AC: 9282 AN: 18412

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 8495 AN: 14196

East Asian (EAS) AF: 0.585 AC: 18275 AN: 31218

South Asian (SAS) AF: 0.672 AC: 30460 AN: 45340

European-Finnish (FIN) AF: 0.591 AC: 24254 AN: 41062

Middle Eastern (MID) AF: 0.661 AC: 2386 AN: 3610

European-Non Finnish (NFE) AF: 0.570 AC: 209463 AN: 367408

Other (OTH) AF: 0.587 AC: 17307 AN: 29508

GnomAD4 genome AF: 0.578 AC: 87914 AN: 152154 Hom.: 25386 Cov.: 33 AF XY: 0.581 AC XY: 43195 AN XY: 74386

African (AFR) AF: 0.572 AC: 23764 AN: 41526

American (AMR) AF: 0.534 AC: 8171 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2005 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3138 AN: 5178

South Asian (SAS) AF: 0.692 AC: 3336 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6377 AN: 10588

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39060 AN: 67962

Other (OTH) AF: 0.609 AC: 1287 AN: 2114

Alfa AF: 0.577 Hom.: 41227

Bravo AF: 0.571

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.73
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7140768; hg19: chr14-20896857; COSMIC: COSV60726811; COSMIC: COSV60726811;