rs2269655

Positions:

• chr1-175166468-C-A
• chr1-175166468-C-T

Variant summary

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

The NM_014656.3(KIAA0040):​c.-134+94G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,190 control chromosomes in the GnomAD database, including 1,396 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 0.12 (1396 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: KIAA0040 NM_014656.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0040	NM_014656.3	c.-134+94G>T		intron_variant		ENST00000423313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0040	ENST00000423313.6	c.-134+94G>T		intron_variant		1	NM_014656.3	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17724 AN: 152042 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0667 AC: 2 AN: 30 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.116 AC: 17722 AN: 152160 Hom.: 1396 Cov.: 32 AF XY: 0.119 AC XY: 8887 AN XY: 74390

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.125

Alfa AF: 0.126 Hom.: 687

Bravo AF: 0.107

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.70

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: rs2269655; hg19: chr1-175135604;