10-24256130-A-T

Variant names:

• chr10-24256130-A-T
• rs2280172
• NM_019590.5:c.354+36221A>T

Variant summary

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

The NM_019590.5(KIAA1217):​c.354+36221A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 150,686 control chromosomes in the GnomAD database, including 39,998 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 0.73 (39998 hom., cov: 27)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019590.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	NM_019590.5	MANE Select	c.354+36221A>T		intron	N/A	NP_062536.2
	KIAA1217	NM_001282767.2		c.354+36221A>T		intron	N/A	NP_001269696.1	Q5T5P2-10
	KIAA1217	NM_001282768.2		c.354+36221A>T		intron	N/A	NP_001269697.1	Q5T5P2-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.354+36221A>T		intron	N/A	ENSP00000365637.3	Q5T5P2-1
	KIAA1217	ENST00000376452.7	TSL:1	c.354+36221A>T		intron	N/A	ENSP00000365635.3	Q5T5P2-10
	KIAA1217	ENST00000458595.5	TSL:1	c.354+36221A>T		intron	N/A	ENSP00000392625.1	Q5T5P2-7

Frequencies

GnomAD3 genomes AF: 0.727 AC: 109427 AN: 150576 Hom.: 39973 Cov.: 27

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.673

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.727 AC: 109498 AN: 150686 Hom.: 39998 Cov.: 27 AF XY: 0.726 AC XY: 53290 AN XY: 73438

African (AFR) AF: 0.704 AC: 28868 AN: 40978

American (AMR) AF: 0.792 AC: 11924 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2709 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3091 AN: 5052

South Asian (SAS) AF: 0.530 AC: 2535 AN: 4782

European-Finnish (FIN) AF: 0.773 AC: 7841 AN: 10138

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.740 AC: 50227 AN: 67908

Other (OTH) AF: 0.711 AC: 1491 AN: 2098

Alfa AF: 0.749 Hom.: 5321

Bravo AF: 0.729

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.70
DANN	Benign	0.80
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2280172;

hg19: chr10-24545059;