rs2885805

Variant names:

• chr1-110875293-C-A
• rs2885805
• NM_000560.4:c.-18+2045C>A

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+2045C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,014 control chromosomes in the GnomAD database, including 6,068 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 0.27 (6068 hom., cov: 32)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 16 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD53	NM_000560.4	c.-18+2045C>A		intron_variant	Intron 1 of 7	ENST00000271324.6	NP_000551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD53	ENST00000271324.6	c.-18+2045C>A		intron_variant	Intron 1 of 7	1	NM_000560.4	ENSP00000271324.5
CD53	ENST00000648608.2	c.-18+2045C>A		intron_variant	Intron 2 of 8			ENSP00000497382.1
CD53	ENST00000471220.5	n.66+2045C>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40500 AN: 151896 Hom.: 6061 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.267 AC: 40529 AN: 152014 Hom.: 6068 Cov.: 32 AF XY: 0.270 AC XY: 20036 AN XY: 74290

African (AFR) AF: 0.143 AC: 5938 AN: 41464

American (AMR) AF: 0.334 AC: 5108 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1526 AN: 5144

South Asian (SAS) AF: 0.394 AC: 1903 AN: 4826

European-Finnish (FIN) AF: 0.293 AC: 3102 AN: 10572

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20239 AN: 67940

Other (OTH) AF: 0.336 AC: 708 AN: 2110

Alfa AF: 0.293 Hom.: 23525

Bravo AF: 0.266

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.65
DANN	Benign	0.69
PhyloP100		-1.8
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: rs2885805; hg19: chr1-111417915;