8-78711382-A-G

Variant names:

• chr8-78711382-A-G
• rs1483573
• NM_016010.3:c.705-3839A>G

Variant summary

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

The NM_016010.3(ZC2HC1A):​c.705-3839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,118 control chromosomes in the GnomAD database, including 33,074 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 0.64 (33074 hom., cov: 29)
• Consequence: ZC2HC1A NM_016010.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 publications found

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]

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

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 = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC2HC1A	NM_016010.3	c.705-3839A>G		intron_variant	Intron 7 of 8	ENST00000263849.9	NP_057094.2
ZC2HC1A	NM_001362969.2	c.705-608A>G		intron_variant	Intron 7 of 9		NP_001349898.1
ZC2HC1A	NR_156423.2	n.765-608A>G		intron_variant	Intron 7 of 10
IL7	XM_011517523.4	c.414+25092T>C		intron_variant	Intron 5 of 5		XP_011515825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC2HC1A	ENST00000263849.9	c.705-3839A>G		intron_variant	Intron 7 of 8	1	NM_016010.3	ENSP00000263849.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97216 AN: 151000 Hom.: 33074 Cov.: 29

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.643 AC: 97241 AN: 151118 Hom.: 33074 Cov.: 29 AF XY: 0.646 AC XY: 47646 AN XY: 73798

African (AFR) AF: 0.410 AC: 16917 AN: 41288

American (AMR) AF: 0.726 AC: 11009 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3466

East Asian (EAS) AF: 0.903 AC: 4649 AN: 5148

South Asian (SAS) AF: 0.730 AC: 3484 AN: 4774

European-Finnish (FIN) AF: 0.735 AC: 7616 AN: 10358

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49446 AN: 67634

Other (OTH) AF: 0.625 AC: 1304 AN: 2086

Alfa AF: 0.702 Hom.: 55776

Bravo AF: 0.638

Asia WGS AF: 0.753 AC: 2610 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.45
PhyloP100		-1.1
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: rs1483573; hg19: chr8-79623617;