rs17604700

Variant names:

• chr15-31842634-C-T
• rs17604700
• NM_001382637.1:c.-100+27873G>A

Variant summary

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

The NM_001382637.1(OTUD7A):​c.-100+27873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,018 control chromosomes in the GnomAD database, including 14,438 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 0.40 (14438 hom., cov: 30)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 3 publications found

Genes affected

OTUD7A (HGNC:20718): (OTU deubiquitinase 7A) The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

OTUD7A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	NM_001382637.1	MANE Select	c.-100+27873G>A		intron	N/A	NP_001369566.1
	OTUD7A	NM_130901.3		c.-223+27873G>A		intron	N/A	NP_570971.1
	OTUD7A	NM_001329907.2		c.-223+27873G>A		intron	N/A	NP_001316836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.-100+27873G>A		intron	N/A	ENSP00000305926.5
	OTUD7A	ENST00000558371.5	TSL:1	n.72+27873G>A		intron	N/A
	OTUD7A	ENST00000560598.2	TSL:5	c.-223+27873G>A		intron	N/A	ENSP00000453883.2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60624 AN: 151900 Hom.: 14437 Cov.: 30

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.399 AC: 60620 AN: 152018 Hom.: 14438 Cov.: 30 AF XY: 0.399 AC XY: 29683 AN XY: 74308

African (AFR) AF: 0.140 AC: 5806 AN: 41486

American (AMR) AF: 0.476 AC: 7277 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1145 AN: 5156

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4814

European-Finnish (FIN) AF: 0.545 AC: 5758 AN: 10574

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

European-Non Finnish (NFE) AF: 0.522 AC: 35433 AN: 67924

Other (OTH) AF: 0.439 AC: 926 AN: 2108

Alfa AF: 0.425 Hom.: 2891

Bravo AF: 0.385

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.093
DANN	Benign	0.83
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs17604700; hg19: chr15-32134837;