Variant chr3-119537173-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005191.4(CD80):c.664C>T(p.His222Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,613,976 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 4 hom., cov: 32)

Exomes 𝑓: 0.010 ( 101 hom. )

Consequence

CD80
NM_005191.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.125

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009736687).

BP6

Variant 3-119537173-G-A is Benign according to our data. Variant chr3-119537173-G-A is described in ClinVar as [Benign]. Clinvar id is 774605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD80	NM_005191.4 linkuse as main transcript	c.664C>T	p.His222Tyr	missense_variant	4/7	ENST00000264246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD80	ENST00000264246.8 linkuse as main transcript	c.664C>T	p.His222Tyr	missense_variant	4/7	1	NM_005191.4	P2	P33681-1
CD80	ENST00000478182.5 linkuse as main transcript	c.664C>T	p.His222Tyr	missense_variant	4/6	1		P2	P33681-1
CD80	ENST00000383669.3 linkuse as main transcript	c.664C>T	p.His222Tyr	missense_variant	3/4	1		A2	P33681-2

Frequencies

GnomAD3 genomes

AF:

0.00761

AC:

1158

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00737

AC:

1850

AN:

251054

Hom.:

AF XY:

0.00725

AC XY:

984

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.0102

AC:

14888

AN:

1461654

Hom.:

101

Cov.:

AF XY:

0.00993

AC XY:

7220

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00613

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00308

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00909

GnomAD4 genome

AF:

0.00760

AC:

1158

AN:

152322

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00795

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0105

AC:

ExAC

AF:

0.00713

AC:

865

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.59

D;D;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.72

.;T;T

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.026

D;D;T

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.81

P;P;.

Vest4

0.21

MVP

0.81

MPC

0.29

ClinPred

0.0064

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.17

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