1-110891000-C-T

Variant names:

• chr1-110891000-C-T
• rs4839583
• NM_000560.4:c.-17-392C>T

Variant summary

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

The NM_000560.4(CD53):​c.-17-392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,210 control chromosomes in the GnomAD database, including 14,500 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 0.40 (14500 hom., cov: 33)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 8 publications found

Genes affected

CD53 (HGNC:1686): (CD53 molecule) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It contributes to the transduction of CD2-generated signals in T cells and natural killer cells and has been suggested to play a role in growth regulation. Familial deficiency of this gene has been linked to an immunodeficiency associated with recurrent infectious diseases caused by bacteria, fungi and viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

LRIF1 (HGNC:30299): (ligand dependent nuclear receptor interacting factor 1) Predicted to enable retinoic acid receptor binding activity. Involved in dosage compensation by inactivation of X chromosome. Located in Barr body; centriolar satellite; and nucleoplasm. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

LRIF1 Gene-Disease associations (from GenCC):

• facioscapulohumeral muscular dystrophy 3, digenic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000304336 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000560.4. 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
	CD53	NM_000560.4	MANE Select	c.-17-392C>T		intron	N/A	NP_000551.1	P19397
	CD53	NM_001040033.2		c.-17-392C>T		intron	N/A	NP_001035122.1	P19397
	CD53	NM_001320638.2		c.-17-392C>T		intron	N/A	NP_001307567.1	B4DQB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD53	ENST00000271324.6	TSL:1 MANE Select	c.-17-392C>T		intron	N/A	ENSP00000271324.5	P19397
	CD53	ENST00000648608.2		c.-17-392C>T		intron	N/A	ENSP00000497382.1	P19397
	CD53	ENST00000897411.1		c.-17-392C>T		intron	N/A	ENSP00000567470.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61497 AN: 152092 Hom.: 14490 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.404 AC: 61519 AN: 152210 Hom.: 14500 Cov.: 33 AF XY: 0.405 AC XY: 30175 AN XY: 74426

African (AFR) AF: 0.147 AC: 6125 AN: 41548

American (AMR) AF: 0.542 AC: 8290 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2188 AN: 5182

South Asian (SAS) AF: 0.412 AC: 1989 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5201 AN: 10592

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34347 AN: 67976

Other (OTH) AF: 0.429 AC: 907 AN: 2116

Alfa AF: 0.428 Hom.: 3301

Bravo AF: 0.399

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs4839583; hg19: chr1-111433622;