10-24275724-C-T

Variant summary

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

The NM_019590.5(KIAA1217):c.354+55815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 531,600 control chromosomes in the GnomAD database, including 1,754 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 0.050 (325 hom., cov: 33)
  • Exomes 𝑓: 0.073 (1429 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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]

MIR603 (HGNC:32859): (microRNA 603) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1217	NM_019590.5	c.354+55815C>T		intron_variant		ENST00000376454.8
MIR603	NR_030334.1	n.40C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1217	ENST00000376454.8	c.354+55815C>T		intron_variant		1	NM_019590.5	A2
MIR603	ENST00000385195.1	n.40C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7664 AN: 152060 Hom.: 323 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0566

GnomAD3 exomes AF: 0.0727 AC: 17624 AN: 242328 Hom.: 988 AF XY: 0.0768 AC XY: 10105 AN XY: 131542

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.0493

Gnomad NFE exome AF: 0.0553

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0727 AC: 27585 AN: 379420 Hom.: 1429 Cov.: 0 AF XY: 0.0789 AC XY: 17052 AN XY: 216056

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0447

Gnomad4 ASJ exome AF: 0.0592

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0665

GnomAD4 genome AF: 0.0504 AC: 7665 AN: 152180 Hom.: 325 Cov.: 33 AF XY: 0.0533 AC XY: 3962 AN XY: 74392

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0560

Alfa AF: 0.0530 Hom.: 387

Bravo AF: 0.0460

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.5
Dann	Benign	0.35

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: rs11014002; hg19: chr10-24564653; COSMIC: COSV64606474;