chr1-53216027-T-G

Position:

• chr1-53216027-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000294360.5(CZIB):​c.369A>C​(p.Ser123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,560 control chromosomes in the GnomAD database, including 33,329 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 0.15 (2170 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31159 hom.)
• Consequence: CZIB ENST00000294360.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

Genes affected

CZIB (HGNC:26059): (CXXC motif containing zinc binding protein) Enables zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CZIB	NM_017887.3	c.369A>C	p.Ser123=	synonymous_variant	7/8	ENST00000294360.5	NP_060357.1
CZIB	NM_001304759.2	c.312A>C	p.Ser104=	synonymous_variant	6/7		NP_001291688.1
CZIB	NM_001304760.2	c.228A>C	p.Ser76=	synonymous_variant	5/6		NP_001291689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CZIB	ENST00000294360.5	c.369A>C	p.Ser123=	synonymous_variant	7/8	1	NM_017887.3	ENSP00000294360	P1
CZIB	ENST00000470385.5	n.611A>C		non_coding_transcript_exon_variant	6/7	1
CZIB	ENST00000478839.1	n.1609A>C		non_coding_transcript_exon_variant	2/3	2
CZIB	ENST00000483739.5	n.1276A>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22981 AN: 152120 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.164 AC: 41184 AN: 251312 Hom.: 3969 AF XY: 0.168 AC XY: 22824 AN XY: 135820

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0800

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.199 AC: 291264 AN: 1461322 Hom.: 31159 Cov.: 32 AF XY: 0.197 AC XY: 143536 AN XY: 726996

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.0655

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.151 AC: 22998 AN: 152238 Hom.: 2170 Cov.: 32 AF XY: 0.144 AC XY: 10738 AN XY: 74430

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.0947

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.187

Alfa AF: 0.192 Hom.: 2062

Bravo AF: 0.153

Asia WGS AF: 0.0710 AC: 250 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs1134688; hg19: chr1-53681699; COSMIC: COSV53758576; COSMIC: COSV53758576;