rs9474614

Variant names:

• chr6-53650148-A-G
• rs9474614
• NM_001003760.5:c.*1450T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003760.5(KLHL31):​c.*1450T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,250 control chromosomes in the GnomAD database, including 2,668 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 0.15 (2668 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KLHL31 NM_001003760.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

Genes affected

KLHL31 (HGNC:21353): (kelch like family member 31) Involved in negative regulation of JNK cascade and negative regulation of protein phosphorylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LINC01564 (HGNC:51361): (long intergenic non-protein coding RNA 1564)

ACMG classification

Verdict is Benign. Variant got -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 = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL31	NM_001003760.5	c.*1450T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000370905.4	NP_001003760.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL31	ENST00000370905	c.*1450T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001003760.5	ENSP00000359942.3
LINC01564	ENST00000701539.1	n.320-16563A>G		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23490 AN: 152130 Hom.: 2666 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.155 AC: 23533 AN: 152248 Hom.: 2668 Cov.: 33 AF XY: 0.157 AC XY: 11657 AN XY: 74458

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0974 Hom.: 319

Bravo AF: 0.165

Asia WGS AF: 0.288 AC: 998 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs9474614; hg19: chr6-53514946;