rs10494122

Positions:

• chr1-110874477-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000560.4(CD53):​c.-18+1229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,134 control chromosomes in the GnomAD database, including 4,645 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 0.23 (4645 hom., cov: 32)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD53	NM_000560.4	c.-18+1229A>C		intron_variant		ENST00000271324.6	NP_000551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD53	ENST00000271324.6	c.-18+1229A>C		intron_variant		1	NM_000560.4	ENSP00000271324	P1
CD53	ENST00000648608.1	c.-18+1229A>C		intron_variant				ENSP00000497382	P1
CD53	ENST00000471220.5	n.66+1229A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34599 AN: 152016 Hom.: 4638 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.227 AC: 34607 AN: 152134 Hom.: 4645 Cov.: 32 AF XY: 0.231 AC XY: 17172 AN XY: 74356

Gnomad4 AFR AF: 0.0942

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.293

Alfa AF: 0.247 Hom.: 1862

Bravo AF: 0.228

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.76

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: rs10494122; hg19: chr1-111417099;