3-119544833-C-T

Variant names:

• chr3-119544833-C-T
• rs2228017
• NM_005191.4:c.135G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005191.4(CD80):​c.135G>A​(p.Val45Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,613,500 control chromosomes in the GnomAD database, including 50,599 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 0.23 (4324 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46275 hom.)
• Consequence: CD80 NM_005191.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 27 publications found

Genes affected

CD80 (HGNC:1700): (CD80 molecule) The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005191.4. 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
	CD80	NM_005191.4	MANE Select	c.135G>A	p.Val45Val	synonymous	Exon 3 of 7	NP_005182.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD80	ENST00000264246.8	TSL:1 MANE Select	c.135G>A	p.Val45Val	synonymous	Exon 3 of 7	ENSP00000264246.3
	CD80	ENST00000478182.5	TSL:1	c.135G>A	p.Val45Val	synonymous	Exon 3 of 6	ENSP00000418364.1
	CD80	ENST00000383669.3	TSL:1	c.135G>A	p.Val45Val	synonymous	Exon 2 of 4	ENSP00000373165.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35489 AN: 151956 Hom.: 4324 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.248 AC: 62097 AN: 250866 AF XY: 0.251

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.250 AC: 365571 AN: 1461426 Hom.: 46275 Cov.: 34 AF XY: 0.251 AC XY: 182464 AN XY: 727032

African (AFR) AF: 0.179 AC: 5978 AN: 33474

American (AMR) AF: 0.204 AC: 9110 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 6841 AN: 26134

East Asian (EAS) AF: 0.308 AC: 12205 AN: 39690

South Asian (SAS) AF: 0.234 AC: 20146 AN: 86246

European-Finnish (FIN) AF: 0.271 AC: 14472 AN: 53416

Middle Eastern (MID) AF: 0.302 AC: 1743 AN: 5768

European-Non Finnish (NFE) AF: 0.252 AC: 280041 AN: 1111592

Other (OTH) AF: 0.249 AC: 15035 AN: 60392

GnomAD4 genome AF: 0.233 AC: 35498 AN: 152074 Hom.: 4324 Cov.: 32 AF XY: 0.233 AC XY: 17347 AN XY: 74340

African (AFR) AF: 0.184 AC: 7624 AN: 41494

American (AMR) AF: 0.237 AC: 3630 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1505 AN: 5162

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4814

European-Finnish (FIN) AF: 0.262 AC: 2771 AN: 10576

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16993 AN: 67960

Other (OTH) AF: 0.242 AC: 510 AN: 2106

Alfa AF: 0.246 Hom.: 7705

Bravo AF: 0.232

Asia WGS AF: 0.252 AC: 876 AN: 3478

EpiCase AF: 0.254

EpiControl AF: 0.261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-1.3
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: rs2228017; hg19: chr3-119263680; COSMIC: COSV51801740;