rs11686881

Variant names:

• chr2-97737384-C-T
• rs11686881
• NM_001079.4:c.1290-89C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-97737384-C-T
• chr2-97737384-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079.4(ZAP70):​c.1290-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,419,926 control chromosomes in the GnomAD database, including 83,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7351 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76088 hom.)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.64
• Publications: 8 publications found

Genes affected

ZAP70 (HGNC:12858): (zeta chain of T cell receptor associated protein kinase 70) This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ZAP70 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to ZAP70 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-97737384-C-T is Benign according to our data. Variant chr2-97737384-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	NM_001079.4	MANE Select	c.1290-89C>T		intron	N/A	NP_001070.2
	ZAP70	NM_001378594.1		c.1290-89C>T		intron	N/A	NP_001365523.1	P43403-1
	ZAP70	NM_207519.2		c.369-89C>T		intron	N/A	NP_997402.1	P43403-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	ENST00000264972.10	TSL:1 MANE Select	c.1290-89C>T		intron	N/A	ENSP00000264972.5	P43403-1
	ZAP70	ENST00000451498.2	TSL:1	c.369-89C>T		intron	N/A	ENSP00000400475.2	P43403-2
	ZAP70	ENST00000463643.5	TSL:1	n.1151-89C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42797 AN: 151904 Hom.: 7343 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.333 AC: 422599 AN: 1267904 Hom.: 76088 AF XY: 0.326 AC XY: 208022 AN XY: 638188

African (AFR) AF: 0.116 AC: 3462 AN: 29902

American (AMR) AF: 0.379 AC: 15887 AN: 41864

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5072 AN: 24526

East Asian (EAS) AF: 0.0975 AC: 3735 AN: 38318

South Asian (SAS) AF: 0.139 AC: 11227 AN: 80550

European-Finnish (FIN) AF: 0.525 AC: 27255 AN: 51884

Middle Eastern (MID) AF: 0.162 AC: 760 AN: 4704

European-Non Finnish (NFE) AF: 0.360 AC: 339318 AN: 942190

Other (OTH) AF: 0.294 AC: 15883 AN: 53966

GnomAD4 genome AF: 0.282 AC: 42814 AN: 152022 Hom.: 7351 Cov.: 32 AF XY: 0.287 AC XY: 21325 AN XY: 74320

African (AFR) AF: 0.125 AC: 5182 AN: 41488

American (AMR) AF: 0.318 AC: 4862 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.109 AC: 566 AN: 5180

South Asian (SAS) AF: 0.128 AC: 616 AN: 4822

European-Finnish (FIN) AF: 0.542 AC: 5713 AN: 10550

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24255 AN: 67928

Other (OTH) AF: 0.246 AC: 517 AN: 2104

Alfa AF: 0.315 Hom.: 10162

Bravo AF: 0.264

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-1.6
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: rs11686881; hg19: chr2-98353847; COSMIC: COSV53858150; COSMIC: COSV53858150;