ENST00000376451.4:c.-97T>G

Variant names:

• chr10-24466694-T-G
• rs16924796
• ENST00000376451.4:c.-97T>G

Variant summary

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

The ENST00000376451.4(KIAA1217):​c.-97T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 985,288 control chromosomes in the GnomAD database, including 3,881 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 0.077 (640 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3241 hom.)
• Consequence: KIAA1217 ENST00000376451.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 0 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.847-6534T>G		intron_variant	Intron 5 of 20	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.847-6534T>G		intron_variant	Intron 5 of 20	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11746 AN: 152156 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0674

GnomAD4 exome AF: 0.0852 AC: 70946 AN: 833014 Hom.: 3241 Cov.: 30 AF XY: 0.0854 AC XY: 32859 AN XY: 384688

African (AFR) AF: 0.00887 AC: 140 AN: 15786

American (AMR) AF: 0.116 AC: 114 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 224 AN: 5152

East Asian (EAS) AF: 0.177 AC: 641 AN: 3626

South Asian (SAS) AF: 0.0459 AC: 756 AN: 16458

European-Finnish (FIN) AF: 0.207 AC: 57 AN: 276

Middle Eastern (MID) AF: 0.0210 AC: 34 AN: 1620

European-Non Finnish (NFE) AF: 0.0877 AC: 66848 AN: 761814

Other (OTH) AF: 0.0781 AC: 2132 AN: 27298

GnomAD4 genome AF: 0.0772 AC: 11755 AN: 152274 Hom.: 640 Cov.: 32 AF XY: 0.0822 AC XY: 6120 AN XY: 74446

African (AFR) AF: 0.0169 AC: 702 AN: 41576

American (AMR) AF: 0.109 AC: 1669 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.177 AC: 915 AN: 5176

South Asian (SAS) AF: 0.0465 AC: 224 AN: 4820

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10598

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0854 AC: 5808 AN: 68030

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0802 Hom.: 74

Bravo AF: 0.0697

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.020
PromoterAI		-0.049	Neutral
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16924796; hg19: chr10-24755623;