chr8-123645970-C-T

Variant names:

• chr8-123645970-C-T
• rs16898671
• NM_001081675.3:c.1515G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001081675.3(KLHL38):​c.1515G>A​(p.Ala505Ala) 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
• Publications: 10 publications found

Genes affected

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

ENSG00000253286 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081675.3. 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
	KLHL38	NM_001081675.3	MANE Select	c.1515G>A	p.Ala505Ala	synonymous	Exon 4 of 4	NP_001075144.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL38	ENST00000684634.1	MANE Select	c.1515G>A	p.Ala505Ala	synonymous	Exon 4 of 4	ENSP00000508228.1
	KLHL38	ENST00000325995.7	TSL:1	c.1515G>A	p.Ala505Ala	synonymous	Exon 3 of 3	ENSP00000321475.7
	ENSG00000253286	ENST00000524355.1	TSL:4	n.245-12279C>T		intron	N/A

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

GnomAD2 exomes AF: 0.127 AC: 31383 AN: 247370 AF XY: 0.130

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 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

African (AFR) AF: 0.213 AC: 7119 AN: 33480

American (AMR) AF: 0.0668 AC: 2986 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3711 AN: 26134

East Asian (EAS) AF: 0.172 AC: 6846 AN: 39700

South Asian (SAS) AF: 0.188 AC: 16259 AN: 86256

European-Finnish (FIN) AF: 0.0847 AC: 4526 AN: 53418

Middle Eastern (MID) AF: 0.126 AC: 727 AN: 5768

European-Non Finnish (NFE) AF: 0.127 AC: 140774 AN: 1111872

Other (OTH) AF: 0.135 AC: 8151 AN: 60388

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

African (AFR) AF: 0.210 AC: 8684 AN: 41446

American (AMR) AF: 0.0801 AC: 1225 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 494 AN: 3466

East Asian (EAS) AF: 0.174 AC: 899 AN: 5164

South Asian (SAS) AF: 0.186 AC: 896 AN: 4806

European-Finnish (FIN) AF: 0.0841 AC: 890 AN: 10586

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8269 AN: 67964

Other (OTH) AF: 0.142 AC: 299 AN: 2106

Alfa AF: 0.131 Hom.: 6038

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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