Genetic Variant CD247:c.*844A>T (chr1-167430837-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198053.3(CD247):c.*844A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 398,660 control chromosomes in the GnomAD database, including 136,198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 51239 hom., cov: 35)

Exomes 𝑓: 0.83 ( 84959 hom. )

Consequence

CD247
NM_198053.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.180

Publications

18 publications found

Variant links:

Genes affected

CD247 (HGNC:1677): (CD247 molecule) The protein encoded by this gene is T-cell receptor zeta, which together with T-cell receptor alpha/beta and gamma/delta heterodimers, and with CD3-gamma, -delta and -epsilon, forms the T-cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CD247 Gene-Disease associations (from GenCC):

immunodeficiency 25
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CD247 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3 link	c.*844A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000362089.10	NP_932170.1	P20963-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10 link	c.*844A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_198053.3	ENSP00000354782.5		P20963-1

Frequencies

GnomAD3 genomes

AF:

0.819

AC:

124589

AN:

152164

Hom.:

51196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.860

Gnomad ASJ

AF:

0.857

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.869

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.836

Gnomad OTH

AF:

0.839

GnomAD4 exome

AF:

0.830

AC:

204472

AN:

246378

Hom.:

84959

Cov.:

AF XY:

0.830

AC XY:

103598

AN XY:

124840

show subpopulations

African (AFR)

AF:

0.758

AC:

5443

AN:

7182

American (AMR)

AF:

0.864

AC:

6427

AN:

7436

Ashkenazi Jewish (ASJ)

AF:

0.860

AC:

7945

AN:

9242

East Asian (EAS)

AF:

0.756

AC:

17301

AN:

22894

South Asian (SAS)

AF:

0.875

AC:

2654

AN:

3032

European-Finnish (FIN)

AF:

0.854

AC:

17790

AN:

20830

Middle Eastern (MID)

AF:

0.854

AC:

1105

AN:

1294

European-Non Finnish (NFE)

AF:

0.836

AC:

132129

AN:

158096

Other (OTH)

AF:

0.835

AC:

13678

AN:

16372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2707

5415

8122

10830

13537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.819

AC:

124685

AN:

152282

Hom.:

51239

Cov.:

AF XY:

0.821

AC XY:

61127

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.759

AC:

31530

AN:

41534

American (AMR)

AF:

0.860

AC:

13159

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

2977

AN:

3472

East Asian (EAS)

AF:

0.765

AC:

3961

AN:

5178

South Asian (SAS)

AF:

0.869

AC:

4193

AN:

4826

European-Finnish (FIN)

AF:

0.860

AC:

9129

AN:

10618

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.836

AC:

56902

AN:

68032

Other (OTH)

AF:

0.840

AC:

1776

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1201

2401

3602

4802

6003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.826

Hom.:

6475

Bravo

AF:

0.816

Asia WGS

AF:

0.807

AC:

2806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.35

(source)

DANN

Benign

0.59

PhyloP100

-0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over