19-18671567-A-G

Variant summary

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

The NM_018316.3(KLHL26):c.*2322A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,190 control chromosomes in the GnomAD database, including 38,503 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 0.70 (38497 hom., cov: 33)
  • Exomes 𝑓: 0.56 (6 hom.)
• Consequence: KLHL26 NM_018316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

Genes affected

KLHL26 (HGNC:25623): (kelch like family member 26)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL26	NM_018316.3	c.*2322A>G		3_prime_UTR_variant	3/3	ENST00000300976.9
KLHL26	NM_001345982.2	c.*2322A>G		3_prime_UTR_variant	4/4
KLHL26	NM_001345983.2	c.*2322A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL26	ENST00000300976.9	c.*2322A>G		3_prime_UTR_variant	3/3	1	NM_018316.3	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106727 AN: 152036 Hom.: 38444 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 0.556 AC: 20 AN: 36 Hom.: 6 Cov.: 0 AF XY: 0.607 AC XY: 17 AN XY: 28

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.702 AC: 106842 AN: 152154 Hom.: 38497 Cov.: 33 AF XY: 0.702 AC XY: 52230 AN XY: 74406

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.663

Alfa AF: 0.625 Hom.: 39218

Bravo AF: 0.704

Asia WGS AF: 0.672 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.0
Dann	Benign	0.61

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: rs876982; hg19: chr19-18782377;