chr1-160712046-C-G

Variant names:

• chr1-160712046-C-G
• rs352685
• NM_001778.4:c.-283G>C

Variant summary

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

The NM_001778.4(CD48):​c.-283G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,902 control chromosomes in the GnomAD database, including 9,836 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 0.35 (9836 hom., cov: 31)
• Consequence: CD48 NM_001778.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 7 publications found

Genes affected

CD48 (HGNC:1683): (CD48 molecule) This gene encodes a member of the CD2 subfamily of immunoglobulin-like receptors which includes SLAM (signaling lymphocyte activation molecules) proteins. The encoded protein is found on the surface of lymphocytes and other immune cells, dendritic cells and endothelial cells, and participates in activation and differentiation pathways in these cells. The encoded protein does not have a transmembrane domain, however, but is held at the cell surface by a GPI anchor via a C-terminal domain which maybe cleaved to yield a soluble form of the receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

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 (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD48	NM_001778.4	c.-283G>C		upstream_gene_variant		ENST00000368046.8	NP_001769.2
CD48	NM_001256030.2	c.-283G>C		upstream_gene_variant			NP_001242959.1
CD48	XM_005245625.1	c.-283G>C		upstream_gene_variant			XP_005245682.1
CD48	XM_017002867.3	c.-283G>C		upstream_gene_variant			XP_016858356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD48	ENST00000368046.8	c.-283G>C		upstream_gene_variant		1	NM_001778.4	ENSP00000357025.3
CD48	ENST00000613788.1	c.-283G>C		upstream_gene_variant		1		ENSP00000484431.1
CD48	ENST00000368045.3	c.-283G>C		upstream_gene_variant		1		ENSP00000357024.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53182 AN: 151784 Hom.: 9837 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.350 AC: 53197 AN: 151902 Hom.: 9836 Cov.: 31 AF XY: 0.357 AC XY: 26543 AN XY: 74268

African (AFR) AF: 0.342 AC: 14142 AN: 41390

American (AMR) AF: 0.350 AC: 5345 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3287 AN: 5146

South Asian (SAS) AF: 0.597 AC: 2875 AN: 4812

European-Finnish (FIN) AF: 0.342 AC: 3615 AN: 10560

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21706 AN: 67956

Other (OTH) AF: 0.335 AC: 704 AN: 2104

Alfa AF: 0.319 Hom.: 925

Bravo AF: 0.348

Asia WGS AF: 0.585 AC: 2034 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	4.5
DANN	Benign	0.61
PhyloP100		1.2
PromoterAI		0.011	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs352685; hg19: chr1-160681836; COSMIC: COSV107459077;