rs11594456

Variant names:

• chr10-24047704-G-T
• rs11594456
• ENST00000376462.5:c.-171+40330G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_001098500.3	c.-171+40330G>T		intron_variant	Intron 2 of 18		NP_001091970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376462.5	c.-171+40330G>T		intron_variant	Intron 2 of 18	1		ENSP00000365645.1
KIAA1217	ENST00000636305.1	c.211+5209G>T		intron_variant	Intron 1 of 1	5		ENSP00000489926.1

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

African (AFR) AF: 0.00657 AC: 273 AN: 41564

American (AMR) AF: 0.0123 AC: 188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4826

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2555 AN: 68008

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

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
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11594456; hg19: chr10-24336633;