8-123652971-C-T

Variant names:

• chr8-123652971-C-T
• rs7387855
• NM_001081675.3:c.-1-44G>A

Variant summary

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

The NM_001081675.3(KLHL38):​c.-1-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 1,537,658 control chromosomes in the GnomAD database, including 527,845 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 0.79 (47252 hom., cov: 31)
  • Exomes 𝑓: 0.83 (480593 hom.)
• Consequence: KLHL38 NM_001081675.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 9 publications found

Genes affected

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

ENSG00000253286 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL38	NM_001081675.3	c.-1-44G>A		intron_variant	Intron 1 of 3	ENST00000684634.1	NP_001075144.2
KLHL38	XM_047421744.1	c.-45G>A		5_prime_UTR_variant	Exon 2 of 4		XP_047277700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL38	ENST00000684634.1	c.-1-44G>A		intron_variant	Intron 1 of 3		NM_001081675.3	ENSP00000508228.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119298 AN: 151926 Hom.: 47237 Cov.: 31

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.790

GnomAD2 exomes AF: 0.783 AC: 146018 AN: 186462 AF XY: 0.788

Gnomad AFR exome AF: 0.702

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.879

Gnomad EAS exome AF: 0.698

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.849

Gnomad OTH exome AF: 0.799

GnomAD4 exome AF: 0.831 AC: 1151740 AN: 1385614 Hom.: 480593 Cov.: 33 AF XY: 0.829 AC XY: 565845 AN XY: 682526

African (AFR) AF: 0.701 AC: 22235 AN: 31728

American (AMR) AF: 0.678 AC: 25352 AN: 37400

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 19333 AN: 21968

East Asian (EAS) AF: 0.728 AC: 28497 AN: 39128

South Asian (SAS) AF: 0.721 AC: 54263 AN: 75276

European-Finnish (FIN) AF: 0.838 AC: 30719 AN: 36678

Middle Eastern (MID) AF: 0.811 AC: 4236 AN: 5222

European-Non Finnish (NFE) AF: 0.851 AC: 920124 AN: 1080604

Other (OTH) AF: 0.816 AC: 46981 AN: 57610

GnomAD4 genome AF: 0.785 AC: 119358 AN: 152044 Hom.: 47252 Cov.: 31 AF XY: 0.780 AC XY: 57963 AN XY: 74318

African (AFR) AF: 0.705 AC: 29225 AN: 41470

American (AMR) AF: 0.719 AC: 10979 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3046 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3661 AN: 5152

South Asian (SAS) AF: 0.695 AC: 3341 AN: 4808

European-Finnish (FIN) AF: 0.826 AC: 8732 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57683 AN: 67986

Other (OTH) AF: 0.788 AC: 1662 AN: 2108

Alfa AF: 0.812 Hom.: 16222

Bravo AF: 0.775

Asia WGS AF: 0.707 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.34
PhyloP100		-0.32
PromoterAI		-0.0070	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7387855; hg19: chr8-124665211; COSMIC: COSV58088452;