rs12144621

Variant names:

• chr1-167484421-C-G
• rs12144621
• NM_198053.3:c.58+33987G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-167484421-C-G
• chr1-167484421-C-T

Variant summary

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

The NM_198053.3(CD247):​c.58+33987G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,114 control chromosomes in the GnomAD database, including 5,101 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 0.25 (5101 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+33987G>C		intron_variant	Intron 1 of 7	ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.58+33987G>C		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37359 AN: 151996 Hom.: 5098 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37379 AN: 152114 Hom.: 5101 Cov.: 32 AF XY: 0.250 AC XY: 18596 AN XY: 74376

African (AFR) AF: 0.173 AC: 7199 AN: 41508

American (AMR) AF: 0.260 AC: 3977 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.537 AC: 2766 AN: 5150

South Asian (SAS) AF: 0.340 AC: 1641 AN: 4828

European-Finnish (FIN) AF: 0.263 AC: 2783 AN: 10588

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16655 AN: 67976

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.245 Hom.: 589

Bravo AF: 0.244

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.53
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12144621; hg19: chr1-167453658;