Genetic Variant CD5:p.Pro146Leu (chr11-61118951-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014207.4(CD5):c.437C>T(p.Pro146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

CD5
NM_014207.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

3 publications found

Variant links:

Genes affected

CD5 (HGNC:1685): (CD5 molecule) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. This protein is a type-I transmembrane glycoprotein found on the surface of thymocytes, T lymphocytes and a subset of B lymphocytes. The encoded protein contains three SRCR domains and may act as a receptor to regulate T-cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

CD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029067159).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD5	NM_014207.4	MANE Select	c.437C>T	p.Pro146Leu	missense	Exon 4 of 11	NP_055022.2	P06127
	CD5	NM_001346456.2		c.266C>T	p.Pro89Leu	missense	Exon 4 of 11	NP_001333385.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD5	ENST00000347785.8	TSL:1 MANE Select	c.437C>T	p.Pro146Leu	missense	Exon 4 of 11	ENSP00000342681.3	P06127
CD5	ENST00000897878.1		c.467C>T	p.Pro156Leu	missense	Exon 5 of 12	ENSP00000567937.1
CD5	ENST00000544014.1	TSL:4	c.437C>T	p.Pro146Leu	missense	Exon 4 of 5	ENSP00000440899.1	F5GYK3

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000594

AC:

149

AN:

250654

AF XY:

0.000531

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000945

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.00135

AC:

1973

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

976

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33478

American (AMR)

AF:

0.000559

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000243

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000938

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00163

AC:

1814

AN:

1111786

Other (OTH)

AF:

0.00119

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

186

278

371

464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

152

228

304

380

<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:

0.000788

AC:

120

AN:

152308

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41564

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

68022

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000839

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00148

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.19

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.75

M_CAP

Benign

0.0072

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

1.6

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.034

Sift

Benign

0.24

Sift4G

Benign

0.18

Polyphen

0.92

Vest4

0.31

MVP

0.55

MPC

0.53

ClinPred

0.027

GERP RS

3.5

Varity_R

0.055

gMVP

0.40

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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