chr10-24521734-C-A

Variant names:

• chr10-24521734-C-A
• rs2297330
• NM_019590.5:c.2309-48C>A

Variant summary

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

The NM_019590.5(KIAA1217):​c.2309-48C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,586,438 control chromosomes in the GnomAD database, including 33,189 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 0.20 (3226 hom., cov: 31)
  • Exomes 𝑓: 0.20 (29963 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	NM_019590.5	MANE Select	c.2309-48C>A		intron	N/A	NP_062536.2
	KIAA1217	NM_001282767.2		c.2204-48C>A		intron	N/A	NP_001269696.1
	KIAA1217	NM_001282768.2		c.2204-48C>A		intron	N/A	NP_001269697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.2309-48C>A		intron	N/A	ENSP00000365637.3
	KIAA1217	ENST00000376451.4	TSL:1	c.1358-48C>A		intron	N/A	ENSP00000365634.2
	KIAA1217	ENST00000376452.7	TSL:1	c.2204-48C>A		intron	N/A	ENSP00000365635.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30555 AN: 151918 Hom.: 3225 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.194 AC: 45525 AN: 235070 AF XY: 0.193

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.0951

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.202 AC: 289795 AN: 1434402 Hom.: 29963 Cov.: 30 AF XY: 0.200 AC XY: 142564 AN XY: 711318

African (AFR) AF: 0.210 AC: 6970 AN: 33256

American (AMR) AF: 0.195 AC: 8631 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5585 AN: 25152

East Asian (EAS) AF: 0.101 AC: 3967 AN: 39322

South Asian (SAS) AF: 0.148 AC: 12469 AN: 84096

European-Finnish (FIN) AF: 0.196 AC: 8518 AN: 43400

Middle Eastern (MID) AF: 0.262 AC: 1492 AN: 5690

European-Non Finnish (NFE) AF: 0.209 AC: 230053 AN: 1099702

Other (OTH) AF: 0.203 AC: 12110 AN: 59590

GnomAD4 genome AF: 0.201 AC: 30554 AN: 152036 Hom.: 3226 Cov.: 31 AF XY: 0.199 AC XY: 14817 AN XY: 74300

African (AFR) AF: 0.201 AC: 8333 AN: 41454

American (AMR) AF: 0.185 AC: 2833 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3468

East Asian (EAS) AF: 0.105 AC: 543 AN: 5148

South Asian (SAS) AF: 0.152 AC: 730 AN: 4814

European-Finnish (FIN) AF: 0.198 AC: 2087 AN: 10560

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14524 AN: 67992

Other (OTH) AF: 0.206 AC: 436 AN: 2114

Alfa AF: 0.213 Hom.: 6264

Bravo AF: 0.203

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0050
DANN	Benign	0.63
PhyloP100		-3.2
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

Other links and lift over

dbSNP: rs2297330; hg19: chr10-24810663; COSMIC: COSV56824489;