rs16857280

Variant names:

• chr2-217310350-G-A
• rs16857280
• ENST00000452813.1:n.394+7565G>A

Variant summary

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

The ENST00000474063.5(DIRC3):​n.2233+7616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,066 control chromosomes in the GnomAD database, including 1,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.11 (1242 hom., cov: 31)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.665
• Publications: 3 publications found

Genes affected

TESHL (HGNC:52740): (testicular germ cell expressed HSF2 interacting lncRNA)

DIRC3 (HGNC:17805): (disrupted in renal carcinoma 3)

DIRC3-AS1 (HGNC:50636): (DIRC3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIRC3	NR_026597.2	n.3065+7616C>T		intron_variant	Intron 12 of 12
DIRC3-AS1	NR_133642.1	n.400+7565G>A		intron_variant	Intron 4 of 5
DIRC3	NR_186292.1	n.4304+7616C>T		intron_variant	Intron 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESHL	ENST00000452813.1	n.394+7565G>A		intron_variant	Intron 4 of 4	3
DIRC3	ENST00000474063.5	n.2233+7616C>T		intron_variant	Intron 11 of 11	2
DIRC3	ENST00000486365.6	n.3065+7616C>T		intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17284 AN: 151948 Hom.: 1241 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17306 AN: 152066 Hom.: 1242 Cov.: 31 AF XY: 0.113 AC XY: 8378 AN XY: 74312

African (AFR) AF: 0.166 AC: 6878 AN: 41478

American (AMR) AF: 0.127 AC: 1941 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1211 AN: 5164

South Asian (SAS) AF: 0.145 AC: 691 AN: 4774

European-Finnish (FIN) AF: 0.0568 AC: 602 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5389 AN: 67986

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.0930 Hom.: 1012

Bravo AF: 0.127

Asia WGS AF: 0.218 AC: 755 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

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Department of Ophthalmology, College of Medicine, Hanyang University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16857280; hg19: chr2-218175073;