1-110886365-C-G

Variant names:

• chr1-110886365-C-G
• rs6679497
• NM_000560.4:c.-17-5027C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000560.4(CD53):​c.-17-5027C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,834 control chromosomes in the GnomAD database, including 15,751 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 0.43 (15751 hom., cov: 30)
• Consequence: CD53 NM_000560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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]

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD53	NM_000560.4	c.-17-5027C>G		intron_variant	Intron 1 of 7	ENST00000271324.6	NP_000551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD53	ENST00000271324.6	c.-17-5027C>G		intron_variant	Intron 1 of 7	1	NM_000560.4	ENSP00000271324.5

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65682 AN: 151716 Hom.: 15738 Cov.: 30

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.433 AC: 65727 AN: 151834 Hom.: 15751 Cov.: 30 AF XY: 0.433 AC XY: 32132 AN XY: 74180

African (AFR) AF: 0.213 AC: 8797 AN: 41384

American (AMR) AF: 0.556 AC: 8491 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2182 AN: 5164

South Asian (SAS) AF: 0.422 AC: 2033 AN: 4816

European-Finnish (FIN) AF: 0.496 AC: 5205 AN: 10496

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35455 AN: 67926

Other (OTH) AF: 0.463 AC: 976 AN: 2108

Alfa AF: 0.464 Hom.: 2148

Bravo AF: 0.430

Asia WGS AF: 0.431 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.38
PhyloP100		0.055
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: rs6679497; hg19: chr1-111428987;