rs867040

chr10-24542576-G-C

Variant summary

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

The NM_019590.5(KIAA1217):c.3535-117G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,538,230 control chromosomes in the GnomAD database, including 38,081 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 0.23 (4063 hom., cov: 33)
  • Exomes 𝑓: 0.22 (34018 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422

Genes affected

KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1217	NM_019590.5	c.3535-117G>C		intron_variant		ENST00000376454.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1217	ENST00000376454.8	c.3535-117G>C		intron_variant		1	NM_019590.5	A2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34453 AN: 152126 Hom.: 4058 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.218 AC: 302167 AN: 1385986 Hom.: 34018 Cov.: 26 AF XY: 0.220 AC XY: 150231 AN XY: 682718

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.226 AC: 34482 AN: 152244 Hom.: 4063 Cov.: 33 AF XY: 0.226 AC XY: 16801 AN XY: 74424

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.263

Alfa AF: 0.225 Hom.: 476

Bravo AF: 0.227

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.36

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: rs867040; hg19: chr10-24831505;