Variant rs1281013 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_001170754.2(C1orf127):c.1290+2C>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,598,944 control chromosomes in the GnomAD database, including 2,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 791 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1675 hom. )

Consequence

C1orf127
NM_001170754.2 splice_donor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Variant links:

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]

C1orf127 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.076860845 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8, offset of 0 (no position change), new splice context is: aaaGTacgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf127	NM_001170754.2 link	c.1290+2C>T		splice_donor_variant, intron_variant		ENST00000377004.9	NP_001164225.1	G8JLG8B7ZLG7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
C1orf127	ENST00000377004.9 link	c.1290+2C>T	splice_donor_variant, intron_variant		5	NM_001170754.2	ENSP00000366203.4	G8JLG8
C1orf127	ENST00000520253.1 link	c.1143+80C>T	intron_variant		5		ENSP00000429704.1	H0YBK5
C1orf127	ENST00000418570.6 link	c.792+2C>T	splice_donor_variant, intron_variant		2		ENSP00000387816.2	H3BM07
C1orf127	ENST00000476357.1 link	n.130C>T	non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0770

AC:

11706

AN:

152112

Hom.:

789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0589

GnomAD3 exomes

AF:

0.0391

AC:

8784

AN:

224452

Hom.:

341

AF XY:

0.0365

AC XY:

4430

AN XY:

121284

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0443

Gnomad EAS exome

AF:

0.00454

Gnomad SAS exome

AF:

0.0281

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0338

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0394

AC:

56948

AN:

1446714

Hom.:

1675

Cov.:

AF XY:

0.0385

AC XY:

27654

AN XY:

718242

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0429

Gnomad4 EAS exome

AF:

0.00319

Gnomad4 SAS exome

AF:

0.0307

Gnomad4 FIN exome

AF:

0.0532

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0771

AC:

11734

AN:

152230

Hom.:

791

Cov.:

AF XY:

0.0750

AC XY:

5579

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.0318

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.00424

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.0571

Gnomad4 NFE

AF:

0.0381

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0435

Hom.:

514

Bravo

AF:

0.0800

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.163

AC:

719

ESP6500EA

AF:

0.0385

AC:

331

ExAC

AF:

0.0395

AC:

4790

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.5

DANN

Benign

0.40

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.023

GERP RS

-0.58

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

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