chr1-167430844-G-C

Variant names:

• chr1-167430844-G-C
• rs1052230
• NM_198053.3:c.*837C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198053.3(CD247):​c.*837C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 398,696 control chromosomes in the GnomAD database, including 4,578 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 0.15 (1703 hom., cov: 33)
  • Exomes 𝑓: 0.15 (2875 hom.)
• Consequence: CD247 NM_198053.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 12 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198053.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	NM_198053.3	MANE Select	c.*837C>G		3_prime_UTR	Exon 8 of 8	NP_932170.1
	CD247	NM_001378515.1		c.*837C>G		3_prime_UTR	Exon 9 of 9	NP_001365444.1
	CD247	NM_001378516.1		c.*837C>G		3_prime_UTR	Exon 9 of 9	NP_001365445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	ENST00000362089.10	TSL:1 MANE Select	c.*837C>G		3_prime_UTR	Exon 8 of 8	ENSP00000354782.5
	CD247	ENST00000392122.4	TSL:1	c.*837C>G		3_prime_UTR	Exon 8 of 8	ENSP00000375969.3
	CD247	ENST00000470379.2	TSL:1	c.*837C>G		3_prime_UTR	Exon 6 of 6	ENSP00000514807.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22153 AN: 152144 Hom.: 1701 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.149 AC: 36775 AN: 246434 Hom.: 2875 Cov.: 0 AF XY: 0.150 AC XY: 18688 AN XY: 124860

African (AFR) AF: 0.163 AC: 1172 AN: 7182

American (AMR) AF: 0.115 AC: 852 AN: 7436

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 1074 AN: 9242

East Asian (EAS) AF: 0.244 AC: 5590 AN: 22894

South Asian (SAS) AF: 0.0986 AC: 299 AN: 3032

European-Finnish (FIN) AF: 0.124 AC: 2593 AN: 20828

Middle Eastern (MID) AF: 0.126 AC: 163 AN: 1294

European-Non Finnish (NFE) AF: 0.144 AC: 22762 AN: 158152

Other (OTH) AF: 0.139 AC: 2270 AN: 16374

GnomAD4 genome AF: 0.146 AC: 22162 AN: 152262 Hom.: 1703 Cov.: 33 AF XY: 0.144 AC XY: 10715 AN XY: 74440

African (AFR) AF: 0.165 AC: 6863 AN: 41548

American (AMR) AF: 0.119 AC: 1817 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1211 AN: 5168

South Asian (SAS) AF: 0.103 AC: 497 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1215 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9745 AN: 68022

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.142 Hom.: 214

Bravo AF: 0.146

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.46
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1052230; hg19: chr1-167400081;