10-24406435-A-G

Variant names:

• chr10-24406435-A-G
• rs991580
• NM_019590.5:c.553+25368A>G

Variant summary

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

The NM_019590.5(KIAA1217):​c.553+25368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,550 control chromosomes in the GnomAD database, including 2,227 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 0.17 (2227 hom., cov: 32)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.553+25368A>G		intron_variant	Intron 3 of 20	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.553+25368A>G		intron_variant	Intron 3 of 20	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25511 AN: 151434 Hom.: 2221 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.169 AC: 25540 AN: 151550 Hom.: 2227 Cov.: 32 AF XY: 0.169 AC XY: 12493 AN XY: 74056

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.179

Alfa AF: 0.176 Hom.: 2397

Bravo AF: 0.162

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.81

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: rs991580; hg19: chr10-24695364;