chr1-167431874-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198053.3(CD247):​c.430-128T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 811,836 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 32 hom., cov: 33)
Exomes 𝑓: 0.022 ( 228 hom. )

Consequence

CD247
NM_198053.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0880
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 1-167431874-A-T is Benign according to our data. Variant chr1-167431874-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0181 (2759/152310) while in subpopulation NFE AF= 0.0275 (1867/68010). AF 95% confidence interval is 0.0264. There are 32 homozygotes in gnomad4. There are 1322 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CD247NM_198053.3 linkuse as main transcriptc.430-128T>A intron_variant ENST00000362089.10 NP_932170.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CD247ENST00000362089.10 linkuse as main transcriptc.430-128T>A intron_variant 1 NM_198053.3 ENSP00000354782 A1P20963-1

Frequencies

GnomAD3 genomes
AF:
0.0181
AC:
2759
AN:
152192
Hom.:
32
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00444
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.0226
Gnomad ASJ
AF:
0.0231
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0110
Gnomad FIN
AF:
0.0143
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0274
Gnomad OTH
AF:
0.0273
GnomAD4 exome
AF:
0.0223
AC:
14740
AN:
659526
Hom.:
228
AF XY:
0.0221
AC XY:
7832
AN XY:
354970
show subpopulations
Gnomad4 AFR exome
AF:
0.00538
Gnomad4 AMR exome
AF:
0.0190
Gnomad4 ASJ exome
AF:
0.0218
Gnomad4 EAS exome
AF:
0.0000284
Gnomad4 SAS exome
AF:
0.0126
Gnomad4 FIN exome
AF:
0.0198
Gnomad4 NFE exome
AF:
0.0275
Gnomad4 OTH exome
AF:
0.0222
GnomAD4 genome
AF:
0.0181
AC:
2759
AN:
152310
Hom.:
32
Cov.:
33
AF XY:
0.0177
AC XY:
1322
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00442
Gnomad4 AMR
AF:
0.0226
Gnomad4 ASJ
AF:
0.0231
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0112
Gnomad4 FIN
AF:
0.0143
Gnomad4 NFE
AF:
0.0275
Gnomad4 OTH
AF:
0.0270
Alfa
AF:
0.0230
Hom.:
5
Asia WGS
AF:
0.00751
AC:
27
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.68
DANN
Benign
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs189198029; hg19: chr1-167401111; API