Genetic Variant CD8A:p.Ala149Ala (chr2-86789707-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001768.7(CD8A):c.447G>A(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,392,202 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 163 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 133 hom. )

Consequence

CD8A
NM_001768.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.641

Publications

0 publications found

Variant links:

Genes affected

CD8A (HGNC:1706): (CD8 subunit alpha) The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 alpha chain. Multiple transcript variants encoding different isoforms have been found for this gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain and thus differ in being a membrane-anchored or secreted protein. [provided by RefSeq, May 2020]

CD8A Gene-Disease associations (from GenCC):

susceptibility to respiratory infections associated with CD8alpha chain mutation
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

CD8A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-86789707-C-T is Benign according to our data. Variant chr2-86789707-C-T is described in ClinVar as Benign. ClinVar VariationId is 464448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.641 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001768.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD8A	NM_001768.7	MANE Select	c.447G>A	p.Ala149Ala	synonymous	Exon 3 of 6	NP_001759.3
CD8A	NM_001145873.1		c.447G>A	p.Ala149Ala	synonymous	Exon 6 of 9	NP_001139345.1
CD8A	NM_001382698.1		c.447G>A	p.Ala149Ala	synonymous	Exon 5 of 8	NP_001369627.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD8A	ENST00000283635.8	TSL:1 MANE Select	c.447G>A	p.Ala149Ala	synonymous	Exon 3 of 6	ENSP00000283635.3
CD8A	ENST00000409511.6	TSL:2	c.447G>A	p.Ala149Ala	synonymous	Exon 6 of 9	ENSP00000386559.2
CD8A	ENST00000352580.7	TSL:2	c.447G>A	p.Ala149Ala	synonymous	Exon 3 of 5	ENSP00000321631.3

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3887

AN:

152140

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00661

AC:

363

AN:

54922

AF XY:

0.00460

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.00705

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00565

GnomAD4 exome

AF:

0.00223

AC:

2767

AN:

1239946

Hom.:

133

Cov.:

AF XY:

0.00192

AC XY:

1161

AN XY:

604598

show subpopulations

African (AFR)

AF:

0.0921

AC:

2309

AN:

25080

American (AMR)

AF:

0.00671

AC:

107

AN:

15954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18780

East Asian (EAS)

AF:

0.00

AC:

AN:

29492

South Asian (SAS)

AF:

0.000309

AC:

AN:

51774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30050

Middle Eastern (MID)

AF:

0.00392

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1012514

Other (OTH)

AF:

0.00555

AC:

284

AN:

51194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0257

AC:

3906

AN:

152256

Hom.:

163

Cov.:

AF XY:

0.0247

AC XY:

1837

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0895

AC:

3720

AN:

41550

American (AMR)

AF:

0.00902

AC:

138

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68008

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

172

344

515

687

859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0136

Hom.:

Bravo

AF:

0.0290

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.8

(source)

DANN

Benign

0.74

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over