rs12661667

Positions:

• chr6-41824807-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286554.2(USP49):​c.-28-17796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,176 control chromosomes in the GnomAD database, including 3,431 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 0.20 (3431 hom., cov: 32)
• Consequence: USP49 NM_001286554.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

Genes affected

USP49 (HGNC:20078): (ubiquitin specific peptidase 49) Enables cysteine-type endopeptidase activity; histone binding activity; and thiol-dependent deubiquitinase. Involved in histone H2B conserved C-terminal lysine deubiquitination and mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288721 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP49	NM_001286554.2	c.-28-17796G>A		intron_variant		ENST00000682992.1	NP_001273483.1
USP49	NM_001384542.1	c.-28-17796G>A		intron_variant			NP_001371471.1
USP49	NM_018561.5	c.-28-17796G>A		intron_variant			NP_061031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP49	ENST00000682992.1	c.-28-17796G>A		intron_variant			NM_001286554.2	ENSP00000507239.1
USP49	ENST00000373010.5	c.-28-17796G>A		intron_variant		5		ENSP00000362101.1
ENSG00000288721	ENST00000684631.1	n.*131-17796G>A		intron_variant				ENSP00000507261.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30734 AN: 152058 Hom.: 3429 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.202 AC: 30743 AN: 152176 Hom.: 3431 Cov.: 32 AF XY: 0.202 AC XY: 15016 AN XY: 74414

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.193

Alfa AF: 0.241 Hom.: 6496

Bravo AF: 0.193

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.47

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: rs12661667; hg19: chr6-41792545;