dbSNP rs2255301: CD4:c.50-31T>C (chr12-6800276-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000616.5(CD4):c.50-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,611,968 control chromosomes in the GnomAD database, including 318,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.61 ( 28733 hom., cov: 28)

Exomes 𝑓: 0.63 ( 289803 hom. )

Consequence

CD4
NM_000616.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374

Publications

17 publications found

Variant links:

Genes affected

CD4 (HGNC:1678): (CD4 molecule) This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 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 II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]

CD4 Gene-Disease associations (from GenCC):

immunodeficiency 79
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-6800276-T-C is Benign according to our data. Variant chr12-6800276-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688003.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD4	NM_000616.5	MANE Select	c.50-31T>C	intron	N/A	NP_000607.1	P01730
CD4	NM_001382707.1		c.50-31T>C	intron	N/A	NP_001369636.1	P01730
CD4	NM_001382714.1		c.49+89T>C	intron	N/A	NP_001369643.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD4	ENST00000011653.9	TSL:1 MANE Select	c.50-31T>C	intron	N/A	ENSP00000011653.4	P01730
CD4	ENST00000541982.5	TSL:1	c.49+89T>C	intron	N/A	ENSP00000445167.1	F5H480
CD4	ENST00000538827.5	TSL:1	n.127+10614T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

92922

AN:

151480

Hom.:

28726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.606

GnomAD2 exomes

AF:

0.595

AC:

149013

AN:

250586

AF XY:

0.592

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.647

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

AF:

0.628

AC:

916622

AN:

1460370

Hom.:

289803

Cov.:

AF XY:

0.623

AC XY:

452853

AN XY:

726550

show subpopulations

African (AFR)

AF:

0.595

AC:

19889

AN:

33442

American (AMR)

AF:

0.514

AC:

22968

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

14865

AN:

26114

East Asian (EAS)

AF:

0.652

AC:

25879

AN:

39678

South Asian (SAS)

AF:

0.477

AC:

41095

AN:

86218

European-Finnish (FIN)

AF:

0.622

AC:

33056

AN:

53120

Middle Eastern (MID)

AF:

0.587

AC:

3386

AN:

5768

European-Non Finnish (NFE)

AF:

0.647

AC:

719000

AN:

1110976

Other (OTH)

AF:

0.604

AC:

36484

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15871

31741

47612

63482

79353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18810

37620

56430

75240

94050

<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:

0.613

AC:

92980

AN:

151598

Hom.:

28733

Cov.:

AF XY:

0.609

AC XY:

45070

AN XY:

74050

show subpopulations

African (AFR)

AF:

0.595

AC:

24580

AN:

41342

American (AMR)

AF:

0.569

AC:

8653

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

1938

AN:

3464

East Asian (EAS)

AF:

0.622

AC:

3194

AN:

5136

South Asian (SAS)

AF:

0.466

AC:

2228

AN:

4780

European-Finnish (FIN)

AF:

0.613

AC:

6421

AN:

10482

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.648

AC:

43979

AN:

67862

Other (OTH)

AF:

0.606

AC:

1278

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1676

3352

5027

6703

8379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.628

Hom.:

8477

Bravo

AF:

0.611

Asia WGS

AF:

0.526

AC:

1827

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

(source)

DANN

Benign

0.67

PhyloP100

-0.37

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over