rs56199250

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198053.3(CD247):c.300+8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,607,538 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 66 hom. )

Consequence

CD247
NM_198053.3 splice_region, intron

Scores

Splicing: ADA: 0.0001641

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0240

Publications

2 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 -20 ACMG points.

BP4

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

BP6

Variant 1-167438562-A-T is Benign according to our data. Variant chr1-167438562-A-T is described in ClinVar as Benign. ClinVar VariationId is 466356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00586 (890/151970) while in subpopulation SAS AF = 0.0121 (58/4796). AF 95% confidence interval is 0.0096. There are 4 homozygotes in GnomAd4. There are 446 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3 link	c.300+8T>A		splice_region_variant, intron_variant	Intron 4 of 7	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.300+8T>A		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_198053.3	ENSP00000354782.5		P20963-1

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

889

AN:

151852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00276

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0121

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.00432

GnomAD2 exomes

AF:

0.00754

AC:

1896

AN:

251478

AF XY:

0.00806

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.00810

Gnomad OTH exome

AF:

0.00879

GnomAD4 exome

AF:

0.00699

AC:

10168

AN:

1455568

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

5305

AN XY:

724570

show subpopulations

African (AFR)

AF:

0.000899

AC:

AN:

33362

American (AMR)

AF:

0.00349

AC:

156

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

326

AN:

26092

East Asian (EAS)

AF:

0.000101

AC:

AN:

39672

South Asian (SAS)

AF:

0.0129

AC:

1113

AN:

86136

European-Finnish (FIN)

AF:

0.0119

AC:

636

AN:

53418

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00669

AC:

7399

AN:

1106218

Other (OTH)

AF:

0.00699

AC:

421

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

523

1045

1568

2090

2613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.00586

AC:

890

AN:

151970

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

446

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41416

American (AMR)

AF:

0.00275

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0121

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.0137

AC:

145

AN:

10584

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00775

AC:

527

AN:

67966

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00824

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00830

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CD247: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 25

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.61

(source)

DANN

Benign

0.63

PhyloP100

-0.024

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.0040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over