chr1-110888466-G-A

Variant names:

• chr1-110888466-G-A
• rs4839581
• NM_000560.4:c.-17-2926G>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.-17-2926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,002 control chromosomes in the GnomAD database, including 33,236 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 0.64 (33236 hom., cov: 31)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 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.-17-2926G>A		intron	N/A	NP_000551.1
	CD53	NM_001040033.2		c.-17-2926G>A		intron	N/A	NP_001035122.1
	CD53	NM_001320638.2		c.-17-2926G>A		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.-17-2926G>A		intron	N/A	ENSP00000271324.5
	CD53	ENST00000648608.2		c.-17-2926G>A		intron	N/A	ENSP00000497382.1
	CD53	ENST00000471220.5	TSL:2	n.67-2926G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97331 AN: 151884 Hom.: 33217 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.641 AC: 97383 AN: 152002 Hom.: 33236 Cov.: 31 AF XY: 0.639 AC XY: 47446 AN XY: 74300

African (AFR) AF: 0.396 AC: 16400 AN: 41454

American (AMR) AF: 0.715 AC: 10924 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2633 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2475 AN: 5170

South Asian (SAS) AF: 0.600 AC: 2884 AN: 4810

European-Finnish (FIN) AF: 0.731 AC: 7707 AN: 10546

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52022 AN: 67970

Other (OTH) AF: 0.665 AC: 1401 AN: 2106

Alfa AF: 0.700 Hom.: 4834

Bravo AF: 0.629

Asia WGS AF: 0.559 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		-0.29
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: rs4839581; hg19: chr1-111431088;