Variant chr8-78698475-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_016010.3(ZC2HC1A):c.666A>G(p.Leu222=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC2HC1A	NM_016010.3 linkuse as main transcript	c.666A>G	p.Leu222=	synonymous_variant	7/9	ENST00000263849.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC2HC1A	ENST00000263849.9 linkuse as main transcript	c.666A>G	p.Leu222=	synonymous_variant	7/9	1	NM_016010.3	P2

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

GnomAD3 exomes

AF:

0.743

AC:

185922

AN:

250396

Hom.:

70173

AF XY:

0.742

AC XY:

100493

AN XY:

135390

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 SAS exome

AF:

0.755

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

Gnomad4 AFR exome

AF:

0.530

Gnomad4 AMR exome

AF:

0.824

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.919

Gnomad4 SAS exome

AF:

0.760

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.747

Gnomad4 OTH exome

AF:

0.723

GnomAD4 genome

AF:

0.686

AC:

104246

AN:

152034

Hom.:

36586

Cov.:

AF XY:

0.688

AC XY:

51104

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.535

Gnomad4 AMR

AF:

0.750

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.738

Gnomad4 NFE

AF:

0.739

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.713

Hom.:

48647

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.8

DANN

Benign

0.78

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over