rs12565727

chr1-10973025-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170754.2(C1orf127):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: C1orf127 NM_001170754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

C1orf127 (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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C1orf127	NM_001170754.2	c.128-2936T>C		intron_variant		ENST00000377004.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf127	ENST00000377004.9	c.128-2936T>C		intron_variant		5	NM_001170754.2	P1
C1orf127	ENST00000520253.1	c.61-2936T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.285

Alfa AF: 0.255 Hom.: 3391

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12565727; hg19: chr1-11033082;