Variant 1-10947824-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170754.2(C1orf127):c.2311C>A(p.Leu771Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,599,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

C1orf127
NM_001170754.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.00

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009769797).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf127	NM_001170754.2 link	c.2311C>A	p.Leu771Ile	missense_variant	12/13	ENST00000377004.9	NP_001164225.1	G8JLG8B7ZLG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf127	ENST00000377004.9 link	c.2311C>A	p.Leu771Ile	missense_variant	12/13	5	NM_001170754.2	ENSP00000366203.4		G8JLG8

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000383

AC:

AN:

245496

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

132974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000888

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.0000475

Gnomad NFE exome

AF:

0.000487

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000303

AC:

438

AN:

1447590

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

246

AN XY:

717328

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000912

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.000300

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000302

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000420

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.2311C>A (p.L771I) alteration is located in exon 12 (coding exon 12) of the C1orf127 gene. This alteration results from a C to A substitution at nucleotide position 2311, causing the leucine (L) at amino acid position 771 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.022

DANN

Benign

0.56

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.26

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.67

REVEL

Benign

0.025

Sift

Benign

0.18

Sift4G

Benign

0.46

Vest4

0.10

MVP

0.048

MPC

0.088

ClinPred

0.017

GERP RS

-7.5

gMVP

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over