rs16898671

chr8-123645970-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001081675.3(KLHL38):c.1515G>A(p.Ala505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,772 control chromosomes in the GnomAD database, including 14,943 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 0.14 (1762 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13181 hom.)
• Consequence: KLHL38 NM_001081675.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

Genes affected

KLHL38 (HGNC:34435): (kelch like family member 38)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL38	NM_001081675.3	c.1515G>A	p.Ala505=	synonymous_variant	4/4	ENST00000684634.1
KLHL38	XM_047421744.1	c.1515G>A	p.Ala505=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL38	ENST00000684634.1	c.1515G>A	p.Ala505=	synonymous_variant	4/4		NM_001081675.3	P1
KLHL38	ENST00000325995.7	c.1515G>A	p.Ala505=	synonymous_variant	3/3	1		P1
	ENST00000652905.1	n.176-20378C>T		intron_variant, non_coding_transcript_variant
	ENST00000524355.1	n.245-12279C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21752 AN: 151914 Hom.: 1760 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.127 AC: 31383 AN: 247370 Hom.: 2221 AF XY: 0.130 AC XY: 17423 AN XY: 134420

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0653

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.0813

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.131 AC: 191099 AN: 1461740 Hom.: 13181 Cov.: 32 AF XY: 0.132 AC XY: 95976 AN XY: 727174

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.0668

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.143 AC: 21774 AN: 152032 Hom.: 1762 Cov.: 31 AF XY: 0.141 AC XY: 10467 AN XY: 74326

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0801

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.142

Alfa AF: 0.128 Hom.: 3125

Bravo AF: 0.146

Asia WGS AF: 0.203 AC: 704 AN: 3478

EpiCase AF: 0.126

EpiControl AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	12
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16898671; hg19: chr8-124658210; COSMIC: COSV58087514;