20-62307707-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007002.4(ADRM1):c.735G>A(p.Ala245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,612,068 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (50 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (51 hom.)
• Consequence: ADRM1 NM_007002.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.92

Genes affected

ADRM1 (HGNC:15759): (ADRM1 26S proteasome ubiquitin receptor) This gene encodes a member of the adhesion regulating molecule 1 protein family. The encoded protein is a component of the proteasome where it acts as a ubiquitin receptor and recruits the deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L5. Increased levels of the encoded protein are associated with increased cell adhesion, which is likely an indirect effect of this intracellular protein. Dysregulation of this gene has been implicated in carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 20-62307707-G-A is Benign according to our data. Variant chr20-62307707-G-A is described in ClinVar as [Benign]. Clinvar id is 777606.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2178/152312) while in subpopulation AFR AF= 0.0476 (1978/41560). AF 95% confidence interval is 0.0458. There are 50 homozygotes in gnomad4. There are 1013 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRM1	NM_007002.4	c.735G>A	p.Ala245=	synonymous_variant	7/10	ENST00000253003.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRM1	ENST00000253003.7	c.735G>A	p.Ala245=	synonymous_variant	7/10	1	NM_007002.4	P1
ADRM1	ENST00000491935.5	c.735G>A	p.Ala245=	synonymous_variant	8/11	5		P1
ADRM1	ENST00000620230.4	c.618G>A	p.Ala206=	synonymous_variant	6/9	5

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2173 AN: 152194 Hom.: 50 Cov.: 34

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00456 AC: 1115 AN: 244478 Hom.: 18 AF XY: 0.00354 AC XY: 471 AN XY: 133172

Gnomad AFR exome AF: 0.0481

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000523

Gnomad OTH exome AF: 0.00402

GnomAD4 exome AF: 0.00200 AC: 2922 AN: 1459756 Hom.: 51 Cov.: 33 AF XY: 0.00177 AC XY: 1285 AN XY: 726194

Gnomad4 AFR exome AF: 0.0489

Gnomad4 AMR exome AF: 0.00439

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000580

Gnomad4 NFE exome AF: 0.000343

Gnomad4 OTH exome AF: 0.00499

GnomAD4 genome AF: 0.0143 AC: 2178 AN: 152312 Hom.: 50 Cov.: 34 AF XY: 0.0136 AC XY: 1013 AN XY: 74480

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00549 Hom.: 4

Bravo AF: 0.0164

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.48
Dann	Benign	0.83

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: rs115525800; hg19: chr20-60882763;