NM_020205.4:c.2103G>T

Variant names:

• chr1-149944286-C-A
• rs56929499
• NM_020205.4:c.2103G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020205.4(OTUD7B):​c.2103G>T​(p.Pro701Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,610,142 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (83 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (76 hom.)
• Consequence: OTUD7B NM_020205.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0990
• Publications: 2 publications found

Genes affected

OTUD7B (HGNC:16683): (OTU deubiquitinase 7B) Enables Lys48-specific deubiquitinase activity and thiol-dependent deubiquitinase. Involved in several processes, including negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of macromolecule metabolic process; and protein deubiquitination. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-149944286-C-A is Benign according to our data. Variant chr1-149944286-C-A is described in ClinVar as Benign. ClinVar VariationId is 791609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.099 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020205.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7B	NM_020205.4	MANE Select	c.2103G>T	p.Pro701Pro	synonymous	Exon 12 of 12	NP_064590.2	Q6GQQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7B	ENST00000581312.6	TSL:1 MANE Select	c.2103G>T	p.Pro701Pro	synonymous	Exon 12 of 12	ENSP00000462729.1	Q6GQQ9-1
	OTUD7B	ENST00000907908.1		c.2130G>T	p.Pro710Pro	synonymous	Exon 12 of 12	ENSP00000577967.1
	OTUD7B	ENST00000907909.1		c.2103G>T	p.Pro701Pro	synonymous	Exon 12 of 12	ENSP00000577968.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3049 AN: 152148 Hom.: 81 Cov.: 31

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0197

GnomAD2 exomes AF: 0.00561 AC: 1375 AN: 244992 AF XY: 0.00427

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.00578

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000866

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00235 AC: 3423 AN: 1457876 Hom.: 76 Cov.: 32 AF XY: 0.00208 AC XY: 1507 AN XY: 724898

African (AFR) AF: 0.0646 AC: 2160 AN: 33434

American (AMR) AF: 0.00632 AC: 281 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000303 AC: 26 AN: 85740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53198

Middle Eastern (MID) AF: 0.00750 AC: 43 AN: 5736

European-Non Finnish (NFE) AF: 0.000519 AC: 576 AN: 1109682

Other (OTH) AF: 0.00560 AC: 337 AN: 60218

GnomAD4 genome AF: 0.0202 AC: 3070 AN: 152266 Hom.: 83 Cov.: 31 AF XY: 0.0191 AC XY: 1421 AN XY: 74444

African (AFR) AF: 0.0672 AC: 2790 AN: 41540

American (AMR) AF: 0.0112 AC: 171 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68016

Other (OTH) AF: 0.0194 AC: 41 AN: 2108

Alfa AF: 0.00527 Hom.: 7

Bravo AF: 0.0222

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		0.099

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: rs56929499; hg19: chr1-149916185;