rs11594456

Positions:

• chr10-24047704-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000376462.5(KIAA1217):​c.-171+40330G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 152,268 control chromosomes in the GnomAD database, including 56 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 0.023 (56 hom., cov: 32)
• Consequence: KIAA1217 ENST00000376462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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=-0.88).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0232 (3532/152268) while in subpopulation SAS AF= 0.0454 (219/4826). AF 95% confidence interval is 0.0405. There are 56 homozygotes in gnomad4. There are 1701 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1217	NM_001098500.3	c.-171+40330G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1217	ENST00000376462.5	c.-171+40330G>T		intron_variant		1		A2
KIAA1217	ENST00000636305.1	c.211+5209G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3528 AN: 152150 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00659

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0232 AC: 3532 AN: 152268 Hom.: 56 Cov.: 32 AF XY: 0.0228 AC XY: 1701 AN XY: 74462

Gnomad4 AFR AF: 0.00657

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0318 Hom.: 8

Bravo AF: 0.0211

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11594456; hg19: chr10-24336633;