1-116533925-G-T

Position:

• chr1-116533925-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001779.3(CD58):​c.628+2040C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,395,176 control chromosomes in the GnomAD database, including 20,905 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 0.16 (2632 hom., cov: 32)
  • Exomes 𝑓: 0.13 (18273 hom.)
• Consequence: CD58 NM_001779.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

NAP1L4P1 (HGNC:39740): (nucleosome assembly protein 1 like 4 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD58	NM_001779.3	c.628+2040C>A		intron_variant		ENST00000369489.10	NP_001770.1
CD58	NM_001144822.2	c.628+2040C>A		intron_variant			NP_001138294.1
NAP1L4P1		n.116533925G>T		intragenic_variant
CD58	NR_026665.2	n.682+2040C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD58	ENST00000369489.10	c.628+2040C>A		intron_variant		1	NM_001779.3	ENSP00000358501.5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23813 AN: 151992 Hom.: 2629 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.131 AC: 162870 AN: 1243066 Hom.: 18273 Cov.: 23 AF XY: 0.136 AC XY: 85390 AN XY: 628140

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.0879

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.157 AC: 23829 AN: 152110 Hom.: 2632 Cov.: 32 AF XY: 0.168 AC XY: 12477 AN XY: 74350

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.157

Alfa AF: 0.127 Hom.: 374

Bravo AF: 0.161

Asia WGS AF: 0.404 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.65

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: rs1016140; hg19: chr1-117076547; COSMIC: COSV59841449;