1-110878805-G-T

Variant names:

• chr1-110878805-G-T
• rs10857833
• NM_000560.4:c.-18+5557G>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.-18+5557G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,974 control chromosomes in the GnomAD database, including 16,616 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 0.44 (16616 hom., cov: 32)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 5 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]

ENSG00000304336 (HGNC:):

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD53	NM_000560.4	MANE Select	c.-18+5557G>T		intron	N/A	NP_000551.1
	CD53	NM_001040033.2		c.-18+5557G>T		intron	N/A	NP_001035122.1
	CD53	NM_001320638.2		c.-18+5557G>T		intron	N/A	NP_001307567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD53	ENST00000271324.6	TSL:1 MANE Select	c.-18+5557G>T		intron	N/A	ENSP00000271324.5
	CD53	ENST00000648608.2		c.-18+5557G>T		intron	N/A	ENSP00000497382.1
	CD53	ENST00000471220.5	TSL:2	n.66+5557G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67427 AN: 151856 Hom.: 16599 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.444 AC: 67485 AN: 151974 Hom.: 16616 Cov.: 32 AF XY: 0.447 AC XY: 33239 AN XY: 74278

African (AFR) AF: 0.223 AC: 9244 AN: 41442

American (AMR) AF: 0.586 AC: 8957 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1925 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3099 AN: 5170

South Asian (SAS) AF: 0.493 AC: 2379 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5156 AN: 10524

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.515 AC: 35021 AN: 67948

Other (OTH) AF: 0.494 AC: 1044 AN: 2114

Alfa AF: 0.500 Hom.: 32467

Bravo AF: 0.444

Asia WGS AF: 0.538 AC: 1863 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.74
DANN	Benign	0.27
PhyloP100		-0.64
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: rs10857833; hg19: chr1-111421427;