chr15-31537504-C-T

Variant names:

• chr15-31537504-C-T
• rs2125623
• NM_001382637.1:c.551-6696G>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.551-6696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,080 control chromosomes in the GnomAD database, including 8,680 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 0.33 (8680 hom., cov: 33)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.551-6696G>A		intron_variant	Intron 5 of 12	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.551-6696G>A		intron_variant	Intron 6 of 13		NP_570971.1
OTUD7A	NM_001329907.2	c.551-6696G>A		intron_variant	Intron 6 of 10		NP_001316836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.551-6696G>A		intron_variant	Intron 5 of 12	1	NM_001382637.1	ENSP00000305926.5
OTUD7A	ENST00000560598.2	c.551-6696G>A		intron_variant	Intron 6 of 13	5		ENSP00000453883.2
OTUD7A	ENST00000678495.1	c.551-6696G>A		intron_variant	Intron 3 of 10			ENSP00000503326.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50024 AN: 151962 Hom.: 8665 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.329 AC: 50079 AN: 152080 Hom.: 8680 Cov.: 33 AF XY: 0.323 AC XY: 24013 AN XY: 74338

African (AFR) AF: 0.429 AC: 17786 AN: 41462

American (AMR) AF: 0.357 AC: 5462 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1732 AN: 5178

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4824

European-Finnish (FIN) AF: 0.219 AC: 2314 AN: 10584

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19715 AN: 67962

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.300 Hom.: 29425

Bravo AF: 0.347

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.069
DANN	Benign	0.61
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2125623; hg19: chr15-31829707;