Genetic Variant NM_005191.4:c.*214T>G (chr3-119525574-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005191.4(CD80):c.*214T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,346 control chromosomes in the GnomAD database, including 51,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51558 hom., cov: 30)

Exomes 𝑓: 0.90 ( 149 hom. )

Consequence

CD80
NM_005191.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.638

Publications

21 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 3-119525574-A-C is Benign according to our data. Variant chr3-119525574-A-C is described in ClinVar as Benign. ClinVar VariationId is 1224718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD80	NM_005191.4 link	c.*214T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000264246.8	NP_005182.1	P33681-1A0N0P2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD80	ENST00000264246.8 link	c.*214T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_005191.4	ENSP00000264246.3		P33681-1

Frequencies

GnomAD3 genomes

AF:

0.823

AC:

124984

AN:

151860

Hom.:

51516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.862

Gnomad FIN

AF:

0.865

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.815

GnomAD4 exome

AF:

0.899

AC:

329

AN:

366

Hom.:

149

Cov.:

AF XY:

0.893

AC XY:

200

AN XY:

224

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.896

AC:

310

AN:

346

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.929

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.823

AC:

125085

AN:

151980

Hom.:

51558

Cov.:

AF XY:

0.825

AC XY:

61256

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.829

AC:

34386

AN:

41458

American (AMR)

AF:

0.778

AC:

11845

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

2531

AN:

3470

East Asian (EAS)

AF:

0.869

AC:

4495

AN:

5172

South Asian (SAS)

AF:

0.863

AC:

4164

AN:

4826

European-Finnish (FIN)

AF:

0.865

AC:

9122

AN:

10550

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55824

AN:

67970

Other (OTH)

AF:

0.814

AC:

1715

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1148

2296

3444

4592

5740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.816

Hom.:

199272

Bravo

AF:

0.815

Asia WGS

AF:

0.849

AC:

2952

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: 25497975) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

(source)

DANN

Benign

0.50

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over