chr1-116558335-A-G

Variant names:

• chr1-116558335-A-G
• rs1335532
• NM_001779.3:c.70+12568T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001779.3(CD58):​c.70+12568T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,914 control chromosomes in the GnomAD database, including 8,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (8549 hom., cov: 32)
• Consequence: CD58 NM_001779.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.140
• Publications: 78 publications found

Genes affected

CD58 (HGNC:1688): (CD58 molecule) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a ligand of the T lymphocyte CD2 protein, and functions in adhesion and activation of T lymphocytes. The protein is localized to the plasma membrane. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

LOC105378925 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-116558335-A-G is Benign according to our data. Variant chr1-116558335-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001779.3. 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
	CD58	NM_001779.3	MANE Select	c.70+12568T>C		intron	N/A	NP_001770.1
	CD58	NM_001144822.2		c.70+12568T>C		intron	N/A	NP_001138294.1
	CD58	NR_026665.2		n.124+12568T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD58	ENST00000369489.10	TSL:1 MANE Select	c.70+12568T>C		intron	N/A	ENSP00000358501.5
	CD58	ENST00000457047.6	TSL:1	c.70+12568T>C		intron	N/A	ENSP00000409080.2
	CD58	ENST00000369487.3	TSL:1	c.70+12568T>C		intron	N/A	ENSP00000358499.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43066 AN: 151796 Hom.: 8517 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.0938

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.284 AC: 43153 AN: 151914 Hom.: 8549 Cov.: 32 AF XY: 0.293 AC XY: 21778 AN XY: 74240

African (AFR) AF: 0.514 AC: 21252 AN: 41384

American (AMR) AF: 0.311 AC: 4758 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 325 AN: 3466

East Asian (EAS) AF: 0.602 AC: 3103 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1848 AN: 4810

European-Finnish (FIN) AF: 0.218 AC: 2297 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8838 AN: 67948

Other (OTH) AF: 0.256 AC: 540 AN: 2108

Alfa AF: 0.189 Hom.: 14011

Bravo AF: 0.300

Asia WGS AF: 0.482 AC: 1670 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.72
PhyloP100		-0.14
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: rs1335532; hg19: chr1-117100957;