chr1-110892713-C-T

Variant names:

• chr1-110892713-C-T
• rs3790722
• NM_000560.4:c.252+180C>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.252+180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 582,906 control chromosomes in the GnomAD database, including 184,131 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 0.72 (41708 hom., cov: 31)
  • Exomes 𝑓: 0.81 (142423 hom.)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 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.252+180C>T		intron	N/A	NP_000551.1	P19397
	CD53	NM_001040033.2		c.252+180C>T		intron	N/A	NP_001035122.1	P19397
	CD53	NM_001320638.2		c.252+180C>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.252+180C>T		intron	N/A	ENSP00000271324.5	P19397
	CD53	ENST00000648608.2		c.252+180C>T		intron	N/A	ENSP00000497382.1	P19397
	CD53	ENST00000897411.1		c.252+180C>T		intron	N/A	ENSP00000567470.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109530 AN: 151930 Hom.: 41682 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.809 AC: 348501 AN: 430858 Hom.: 142423 Cov.: 4 AF XY: 0.808 AC XY: 182876 AN XY: 226334

African (AFR) AF: 0.451 AC: 5346 AN: 11842

American (AMR) AF: 0.818 AC: 12392 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 10959 AN: 13046

East Asian (EAS) AF: 0.673 AC: 19886 AN: 29552

South Asian (SAS) AF: 0.754 AC: 29804 AN: 39520

European-Finnish (FIN) AF: 0.814 AC: 26127 AN: 32116

Middle Eastern (MID) AF: 0.858 AC: 1629 AN: 1898

European-Non Finnish (NFE) AF: 0.846 AC: 222465 AN: 262806

Other (OTH) AF: 0.798 AC: 19893 AN: 24934

GnomAD4 genome AF: 0.721 AC: 109596 AN: 152048 Hom.: 41708 Cov.: 31 AF XY: 0.720 AC XY: 53542 AN XY: 74354

African (AFR) AF: 0.455 AC: 18851 AN: 41412

American (AMR) AF: 0.797 AC: 12180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3411 AN: 5164

South Asian (SAS) AF: 0.728 AC: 3510 AN: 4822

European-Finnish (FIN) AF: 0.821 AC: 8680 AN: 10578

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57442 AN: 68000

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.809 Hom.: 59295

Bravo AF: 0.707

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.40
PhyloP100		-0.56
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: rs3790722; hg19: chr1-111435335;