dbSNP rs1599795: CD80:c.*780A>T (chr3-119525008-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005191.4(CD80):c.*780A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,210 control chromosomes in the GnomAD database, including 2,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2345 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CD80
NM_005191.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.838

Variant links:

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]

CD80 links:

TIMMDC1 (HGNC:1321): (translocase of inner mitochondrial membrane domain containing 1) Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Apr 2022]

TIMMDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 3-119525008-T-A is Benign according to our data. Variant chr3-119525008-T-A is described in ClinVar as [Benign]. Clinvar id is 1288301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CD80	NM_005191.4 link	c.*780A>T	3_prime_UTR_variant	Exon 7 of 7	ENST00000264246.8	NP_005182.1	P33681-1A0N0P2
TIMMDC1	NM_016589.4 link	c.*1252T>A	3_prime_UTR_variant	Exon 7 of 7	ENST00000494664.6	NP_057673.2	Q9NPL8
TIMMDC1	XM_017006556.2 link	c.*1252T>A	3_prime_UTR_variant	Exon 3 of 3		XP_016862045.1	C9JU35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD80	ENST00000264246 link	c.*780A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_005191.4	ENSP00000264246.3		P33681-1
TIMMDC1	ENST00000494664.6 link	c.*1252T>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_016589.4	ENSP00000418803.1		Q9NPL8

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23429

AN:

152090

Hom.:

2343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.154

AC:

23436

AN:

152208

Hom.:

2345

Cov.:

AF XY:

0.158

AC XY:

11790

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.158

Hom.:

278

Bravo

AF:

0.146

Asia WGS

AF:

0.202

AC:

704

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24981235) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over