Genetic Variant CD96:p.Thr44Ile (chr3-111545115-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005816.5(CD96):c.131C>T(p.Thr44Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,614,190 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 4 hom. )

Consequence

CD96
NM_005816.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0540

Publications

0 publications found

Variant links:

Genes affected

CD96 (HGNC:16892): (CD96 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

CD96 Gene-Disease associations (from GenCC):

C syndrome
Inheritance: AD, Unknown, AR Classification: LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

CD96 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02814272).

BP6

Variant 3-111545115-C-T is Benign according to our data. Variant chr3-111545115-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2715386.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 Unknown,AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD96	NM_005816.5	MANE Select	c.131C>T	p.Thr44Ile	missense	Exon 2 of 14	NP_005807.1	P40200-2
CD96	NM_198196.3		c.131C>T	p.Thr44Ile	missense	Exon 2 of 15	NP_937839.1	P40200-1
CD96	NM_001410800.1		c.131C>T	p.Thr44Ile	missense	Exon 2 of 14	NP_001397729.1	E9PEJ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD96	ENST00000352690.9	TSL:1 MANE Select	c.131C>T	p.Thr44Ile	missense	Exon 2 of 14	ENSP00000342040.3	P40200-2
CD96	ENST00000283285.10	TSL:1	c.131C>T	p.Thr44Ile	missense	Exon 2 of 15	ENSP00000283285.5	P40200-1
CD96	ENST00000438817.6	TSL:1	c.131C>T	p.Thr44Ile	missense	Exon 2 of 8	ENSP00000389801.2	Q8WUE2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000371

AC:

AN:

250460

AF XY:

0.000524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

224

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00347

AC:

299

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111998

Other (OTH)

AF:

0.000182

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000125

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41578

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00373

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000346

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.79

M_CAP

Benign

0.028

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

PhyloP100

-0.054

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.033

Polyphen

0.99

Vest4

0.20

MutPred

0.49

Loss of sheet (P = 0.0817)

MVP

0.31

MPC

0.16

ClinPred

0.15

GERP RS

4.3

Varity_R

0.19

gMVP

0.60

Mutation Taster

=97/3

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