rs6554

Variant names:

• chr19-18575154-G-T
• rs6554
• NM_001033930.3:c.*4G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-18575154-G-T
• chr19-18575154-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033930.3(UBA52):​c.*4G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,613,814 control chromosomes in the GnomAD database, including 307,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.69 (37721 hom., cov: 32)
  • Exomes 𝑓: 0.60 (269949 hom.)
• Consequence: UBA52 NM_001033930.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 31 publications found

Genes affected

UBA52 (HGNC:12458): (ubiquitin A-52 residue ribosomal protein fusion product 1) Ubiquitin is a highly conserved nuclear and cytoplasmic protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein L40 at the C terminus, a C-terminal extension protein (CEP). Multiple processed pseudogenes derived from this gene are present in the genome. [provided by RefSeq, Jul 2008]

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

CRLF1 Gene-Disease associations (from GenCC):

• Cold-induced sweating syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• cold-induced sweating syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• idiopathic achalasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033930.3. 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
	UBA52	NM_001033930.3	MANE Select	c.*4G>T		3_prime_UTR	Exon 5 of 5	NP_001029102.1	P62987
	UBA52	NM_001321021.1		c.*4G>T		3_prime_UTR	Exon 5 of 5	NP_001307950.1	Q7Z4P3
	UBA52	NM_001321017.2		c.*4G>T		3_prime_UTR	Exon 5 of 5	NP_001307946.1	Q3MIH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA52	ENST00000442744.7	TSL:1 MANE Select	c.*4G>T		3_prime_UTR	Exon 5 of 5	ENSP00000388107.1	P62987
	UBA52	ENST00000430157.6	TSL:1	c.*4G>T		3_prime_UTR	Exon 5 of 5	ENSP00000396910.1	P62987
	UBA52	ENST00000597451.5	TSL:1	c.*4G>T		3_prime_UTR	Exon 4 of 4	ENSP00000473048.1	P62987

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104815 AN: 151994 Hom.: 37648 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.654

GnomAD2 exomes AF: 0.614 AC: 154345 AN: 251204 AF XY: 0.599

Gnomad AFR exome AF: 0.921

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.672

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.577

GnomAD4 exome AF: 0.604 AC: 883189 AN: 1461702 Hom.: 269949 Cov.: 59 AF XY: 0.598 AC XY: 435190 AN XY: 727144

African (AFR) AF: 0.921 AC: 30828 AN: 33476

American (AMR) AF: 0.661 AC: 29543 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 13185 AN: 26130

East Asian (EAS) AF: 0.662 AC: 26299 AN: 39700

South Asian (SAS) AF: 0.488 AC: 42079 AN: 86246

European-Finnish (FIN) AF: 0.622 AC: 33210 AN: 53380

Middle Eastern (MID) AF: 0.506 AC: 2909 AN: 5744

European-Non Finnish (NFE) AF: 0.601 AC: 668212 AN: 1111918

Other (OTH) AF: 0.611 AC: 36924 AN: 60390

GnomAD4 genome AF: 0.690 AC: 104953 AN: 152112 Hom.: 37721 Cov.: 32 AF XY: 0.687 AC XY: 51095 AN XY: 74356

African (AFR) AF: 0.913 AC: 37927 AN: 41532

American (AMR) AF: 0.650 AC: 9931 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1682 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3387 AN: 5164

South Asian (SAS) AF: 0.491 AC: 2366 AN: 4818

European-Finnish (FIN) AF: 0.622 AC: 6585 AN: 10594

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40961 AN: 67936

Other (OTH) AF: 0.657 AC: 1384 AN: 2108

Alfa AF: 0.611 Hom.: 54985

Bravo AF: 0.703

Asia WGS AF: 0.630 AC: 2194 AN: 3478

EpiCase AF: 0.588

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.49
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6554; hg19: chr19-18685964; COSMIC: COSV70615103; COSMIC: COSV70615103;