14-101566903-T-C

Variant names:

• chr14-101566903-T-C
• rs17716499
• ENST00000700197.1:n.925-53A>G

Variant summary

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

The ENST00000700197.1(DIO3OS):​n.925-53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,066 control chromosomes in the GnomAD database, including 10,007 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 0.36 (10007 hom., cov: 32)
• Consequence: DIO3OS ENST00000700197.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 5 publications found

Genes affected

DIO3OS (HGNC:20348): (DIO3 opposite strand upstream RNA) The mouse and human DIO3OS and DIO3 (MIM 601038) genes overlap and are transcribed in opposite directions. The mouse Dio3 gene is imprinted from the paternal allele during fetal development, suggesting that DIO3OS is a noncoding gene that may have a role in maintaining monoallelic expression of DIO3 (Hernandez et al., 2004 [PubMed 14962667]).[supplied by OMIM, Mar 2008]

LOC105370675 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370675	XR_944225.3	n.371-53A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIO3OS	ENST00000700197.1	n.925-53A>G		intron_variant	Intron 6 of 8

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54445 AN: 151948 Hom.: 9996 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.358 AC: 54470 AN: 152066 Hom.: 10007 Cov.: 32 AF XY: 0.358 AC XY: 26636 AN XY: 74322

African (AFR) AF: 0.311 AC: 12892 AN: 41488

American (AMR) AF: 0.322 AC: 4921 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1240 AN: 5144

South Asian (SAS) AF: 0.392 AC: 1885 AN: 4808

European-Finnish (FIN) AF: 0.380 AC: 4022 AN: 10580

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26781 AN: 67958

Other (OTH) AF: 0.386 AC: 816 AN: 2116

Alfa AF: 0.377 Hom.: 26199

Bravo AF: 0.351

Asia WGS AF: 0.310 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs17716499; hg19: chr14-102033240; COSMIC: COSV63773827;