NM_019590.5:c.3535-117G>C

Variant names:

• chr10-24542576-G-C
• rs867040
• NM_019590.5:c.3535-117G>C

Variant summary

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

The NM_019590.5(KIAA1217):​c.3535-117G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,538,230 control chromosomes in the GnomAD database, including 38,081 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 0.23 (4063 hom., cov: 33)
  • Exomes 𝑓: 0.22 (34018 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 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.3535-117G>C		intron	N/A	NP_062536.2
	KIAA1217	NM_001282767.2		c.3427-117G>C		intron	N/A	NP_001269696.1
	KIAA1217	NM_001282768.2		c.3430-2405G>C		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.3535-117G>C		intron	N/A	ENSP00000365637.3
	KIAA1217	ENST00000376451.4	TSL:1	c.2584-117G>C		intron	N/A	ENSP00000365634.2
	KIAA1217	ENST00000376452.7	TSL:1	c.3427-117G>C		intron	N/A	ENSP00000365635.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34453 AN: 152126 Hom.: 4058 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.218 AC: 302167 AN: 1385986 Hom.: 34018 Cov.: 26 AF XY: 0.220 AC XY: 150231 AN XY: 682718

African (AFR) AF: 0.223 AC: 7064 AN: 31700

American (AMR) AF: 0.171 AC: 6264 AN: 36546

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8101 AN: 23902

East Asian (EAS) AF: 0.137 AC: 5093 AN: 37176

South Asian (SAS) AF: 0.246 AC: 18798 AN: 76266

European-Finnish (FIN) AF: 0.187 AC: 9315 AN: 49854

Middle Eastern (MID) AF: 0.365 AC: 1991 AN: 5448

European-Non Finnish (NFE) AF: 0.218 AC: 232240 AN: 1067602

Other (OTH) AF: 0.231 AC: 13301 AN: 57492

GnomAD4 genome AF: 0.226 AC: 34482 AN: 152244 Hom.: 4063 Cov.: 33 AF XY: 0.226 AC XY: 16801 AN XY: 74424

African (AFR) AF: 0.226 AC: 9389 AN: 41524

American (AMR) AF: 0.230 AC: 3517 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.142 AC: 739 AN: 5190

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4822

European-Finnish (FIN) AF: 0.183 AC: 1938 AN: 10602

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15607 AN: 68014

Other (OTH) AF: 0.263 AC: 557 AN: 2114

Alfa AF: 0.225 Hom.: 476

Bravo AF: 0.227

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.36
PhyloP100		-0.42
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: rs867040; hg19: chr10-24831505;