rs3748215

Positions:

• chr10-24473536-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019590.5(KIAA1217):​c.1155A>G​(p.Ala385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,008 control chromosomes in the GnomAD database, including 10,875 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 0.093 (937 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9938 hom.)
• Consequence: KIAA1217 NM_019590.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.79

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-4.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.1155A>G	p.Ala385=	synonymous_variant	6/21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.1155A>G	p.Ala385=	synonymous_variant	6/21	1	NM_019590.5	ENSP00000365637	A2

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14076 AN: 152048 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0790

GnomAD3 exomes AF: 0.109 AC: 27359 AN: 251174 Hom.: 2005 AF XY: 0.106 AC XY: 14361 AN XY: 135744

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.0370

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.109 AC: 159350 AN: 1461842 Hom.: 9938 Cov.: 33 AF XY: 0.107 AC XY: 77570 AN XY: 727216

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0583

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0955

GnomAD4 genome AF: 0.0926 AC: 14090 AN: 152166 Hom.: 937 Cov.: 32 AF XY: 0.0993 AC XY: 7383 AN XY: 74380

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0551

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0950 Hom.: 410

Bravo AF: 0.0803

Asia WGS AF: 0.0840 AC: 291 AN: 3478

EpiCase AF: 0.0935

EpiControl AF: 0.0922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.044
DANN	Benign	0.40

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: rs3748215; hg19: chr10-24762465; COSMIC: COSV56823401;