chr1-116558335-A-G

Position:

• chr1-116558335-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD58	NM_001779.3	c.70+12568T>C		intron_variant		ENST00000369489.10
LOC105378925	XR_947739.2	n.8158A>G		non_coding_transcript_exon_variant	3/3
CD58	NM_001144822.2	c.70+12568T>C		intron_variant
CD58	NR_026665.2	n.124+12568T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD58	ENST00000369489.10	c.70+12568T>C		intron_variant		1	NM_001779.3	A2
CD58	ENST00000369487.3	c.70+12568T>C		intron_variant		1		P4
CD58	ENST00000457047.6	c.70+12568T>C		intron_variant		1		A2
CD58	ENST00000464088.5	c.70+12568T>C		intron_variant, NMD_transcript_variant		1

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

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.0938

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.256

Alfa AF: 0.172 Hom.: 4725

Bravo AF: 0.300

Asia WGS AF: 0.482 AC: 1670 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2019

This variant is associated with the following publications: (PMID: 24655566, 21833088, 30006149) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.72

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: rs1335532; hg19: chr1-117100957;