1-110892713-C-T

Variant names:

• chr1-110892713-C-T
• rs3790722
• NM_000560.4:c.252+180C>T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD53	NM_000560.4	c.252+180C>T		intron_variant	Intron 3 of 7	ENST00000271324.6	NP_000551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD53	ENST00000271324.6	c.252+180C>T		intron_variant	Intron 3 of 7	1	NM_000560.4	ENSP00000271324.5
CD53	ENST00000648608.1	c.252+180C>T		intron_variant	Intron 4 of 8			ENSP00000497382.1
CD53	ENST00000471220.5	n.515C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
CD53	ENST00000476408.1	n.365+180C>T		intron_variant	Intron 3 of 3	5

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

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.846

Gnomad4 OTH exome AF: 0.798

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

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.757

Alfa AF: 0.825 Hom.: 45820

Bravo AF: 0.707

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs3790722; hg19: chr1-111435335;