1-110874477-A-C

Variant names:

• chr1-110874477-A-C
• rs10494122
• NM_000560.4:c.-18+1229A>C

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+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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.-18+1229A>C		intron	N/A	NP_000551.1
	CD53	NM_001040033.2		c.-18+1229A>C		intron	N/A	NP_001035122.1
	CD53	NM_001320638.2		c.-18+1229A>C		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.-18+1229A>C		intron	N/A	ENSP00000271324.5
	CD53	ENST00000648608.2		c.-18+1229A>C		intron	N/A	ENSP00000497382.1
	CD53	ENST00000471220.5	TSL:2	n.66+1229A>C		intron	N/A

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

African (AFR) AF: 0.0942 AC: 3913 AN: 41532

American (AMR) AF: 0.304 AC: 4647 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1527 AN: 5160

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4826

European-Finnish (FIN) AF: 0.254 AC: 2683 AN: 10578

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17880 AN: 67966

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.247 Hom.: 2243

Bravo AF: 0.228

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.051
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: rs10494122; hg19: chr1-111417099;