15-31537504-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.551-6696G>A		intron_variant		ENST00000307050.6
OTUD7A	NM_001329907.2	c.551-6696G>A		intron_variant
OTUD7A	NM_130901.3	c.551-6696G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.551-6696G>A		intron_variant		1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.551-6696G>A		intron_variant		5		A2
OTUD7A	ENST00000678495.1	c.551-6696G>A		intron_variant				A2

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

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.311

Alfa AF: 0.288 Hom.: 12130

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2125623; hg19: chr15-31829707;