rs12565727

Variant names:

• chr1-10973025-A-G
• rs12565727
• NM_001170754.2:c.128-2936T>C

Variant summary

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

The NM_001170754.2(CIROZ):​c.128-2936T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,972 control chromosomes in the GnomAD database, including 7,999 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 0.31 (7999 hom., cov: 32)
• Consequence: CIROZ NM_001170754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 25 publications found

Genes affected

CIROZ (HGNC:26730): (chromosome 1 open reading frame 127) Predicted to be involved in heart development. Predicted to act upstream of or within determination of left/right symmetry. [provided by Alliance of Genome Resources, Apr 2022]

CIROZ Gene-Disease associations (from GenCC):

• visceral heterotaxy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROZ	NM_001170754.2	c.128-2936T>C		intron_variant	Intron 2 of 12	ENST00000377004.9	NP_001164225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf127	ENST00000377004.9	c.128-2936T>C		intron_variant	Intron 2 of 12	5	NM_001170754.2	ENSP00000366203.4
C1orf127	ENST00000520253.1	c.59-2936T>C		intron_variant	Intron 1 of 11	5		ENSP00000429704.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46358 AN: 151854 Hom.: 7986 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.305 AC: 46416 AN: 151972 Hom.: 7999 Cov.: 32 AF XY: 0.305 AC XY: 22691 AN XY: 74286

African (AFR) AF: 0.466 AC: 19283 AN: 41384

American (AMR) AF: 0.250 AC: 3827 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1593 AN: 5172

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3338 AN: 10550

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15538 AN: 67972

Other (OTH) AF: 0.285 AC: 602 AN: 2114

Alfa AF: 0.257 Hom.: 15064

Bravo AF: 0.310

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.0
DANN	Benign	0.22
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12565727; hg19: chr1-11033082;