rs1054283

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP7BA1

The NM_016010.3(ZC2HC1A):c.666A>G(p.Leu222Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,610,586 control chromosomes in the GnomAD database, including 443,631 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 0.69 ( 36586 hom., cov: 32)

Exomes 𝑓: 0.74 ( 407045 hom. )

Consequence

ZC2HC1A
NM_016010.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377

Publications

31 publications found

Variant links:

Genes affected

ZC2HC1A (HGNC:24277): (zinc finger C2HC-type containing 1A) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZC2HC1A links:

IL7 (HGNC:6023): (interleukin 7) The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL7 is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. IL7 plays an essential role in lymphoid cell survival, and in the maintenance of naive and memory T cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their presence in normal tissues has not been confirmed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be a potent inducer of proinflammatory cytokines and chemokines which may defend against the infection, but may also mediate destructive lung injury. Elevated serum IL7 levels, together with several other circulating cytokines and chemokines, has been found to be associated with the severity of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Jul 2020]

IL7 Gene-Disease associations (from GenCC):

epidermodysplasia verruciformis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
epidermodysplasia verruciformis, susceptibility to, 5
Inheritance: AR Classification: LIMITED Submitted by: G2P

IL7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.284).

BP7

Synonymous conserved (PhyloP=0.377 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016010.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC2HC1A	NM_016010.3	MANE Select	c.666A>G	p.Leu222Leu	synonymous	Exon 7 of 9	NP_057094.2	Q96GY0
ZC2HC1A	NM_001362969.2		c.666A>G	p.Leu222Leu	synonymous	Exon 7 of 10	NP_001349898.1	H0YAP0
ZC2HC1A	NR_156423.2		n.726A>G		non_coding_transcript_exon	Exon 7 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC2HC1A	ENST00000263849.9	TSL:1 MANE Select	c.666A>G	p.Leu222Leu	synonymous	Exon 7 of 9	ENSP00000263849.3	Q96GY0
ZC2HC1A	ENST00000519307.2	TSL:5	c.666A>G	p.Leu222Leu	synonymous	Exon 7 of 10	ENSP00000427797.2	H0YAP0
ZC2HC1A	ENST00000874954.1		c.663A>G	p.Leu221Leu	synonymous	Exon 7 of 9	ENSP00000545013.1

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104184

AN:

151916

Hom.:

36568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.667

GnomAD2 exomes

AF:

0.743

AC:

185922

AN:

250396

AF XY:

0.742

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.835

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.911

Gnomad FIN exome

AF:

0.723

Gnomad NFE exome

AF:

0.734

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.745

AC:

1086231

AN:

1458552

Hom.:

407045

Cov.:

AF XY:

0.745

AC XY:

540429

AN XY:

725712

show subpopulations

African (AFR)

AF:

0.530

AC:

17698

AN:

33364

American (AMR)

AF:

0.824

AC:

36743

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

15123

AN:

26076

East Asian (EAS)

AF:

0.919

AC:

36417

AN:

39616

South Asian (SAS)

AF:

0.760

AC:

65338

AN:

86008

European-Finnish (FIN)

AF:

0.730

AC:

38930

AN:

53348

Middle Eastern (MID)

AF:

0.610

AC:

3506

AN:

5744

European-Non Finnish (NFE)

AF:

0.747

AC:

828915

AN:

1109576

Other (OTH)

AF:

0.723

AC:

43561

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

13331

26662

39992

53323

66654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20258

40516

60774

81032

101290

<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:

0.686

AC:

104246

AN:

152034

Hom.:

36586

Cov.:

AF XY:

0.688

AC XY:

51104

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.535

AC:

22164

AN:

41454

American (AMR)

AF:

0.750

AC:

11458

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1976

AN:

3470

East Asian (EAS)

AF:

0.906

AC:

4694

AN:

5180

South Asian (SAS)

AF:

0.765

AC:

3684

AN:

4818

European-Finnish (FIN)

AF:

0.738

AC:

7803

AN:

10572

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50193

AN:

67958

Other (OTH)

AF:

0.667

AC:

1407

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1601

3201

4802

6402

8003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.715

Hom.:

117683

Bravo

AF:

0.683

Asia WGS

AF:

0.793

AC:

2754

AN:

3476

EpiCase

AF:

0.722

EpiControl

AF:

0.715

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.8

(source)

DANN

Benign

0.78

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over