rs1129942

Positions:

• chr1-172468452-G-A
• chr1-172468452-G-C
• chr1-172468452-G-T

Variant summary

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

The NM_139240.4(C1orf105):​c.410G>A​(p.Ser137Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,608,462 control chromosomes in the GnomAD database, including 510,662 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.78 (46506 hom., cov: 32)
  • Exomes 𝑓: 0.80 (464156 hom.)
• Consequence: C1orf105 NM_139240.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

Genes affected

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3782754E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf105	NM_139240.4	c.410G>A	p.Ser137Asn	missense_variant	7/7	ENST00000367727.9	NP_640333.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf105	ENST00000367727.9	c.410G>A	p.Ser137Asn	missense_variant	7/7	1	NM_139240.4	ENSP00000356700	P1
C1orf105	ENST00000367725.4	c.380G>A	p.Ser127Asn	missense_variant	5/5	2		ENSP00000356698
C1orf105	ENST00000367726.1	n.214G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118472 AN: 152008 Hom.: 46486 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.814

GnomAD3 exomes AF: 0.827 AC: 206356 AN: 249618 Hom.: 86142 AF XY: 0.830 AC XY: 112069 AN XY: 135008

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.892

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.902

Gnomad FIN exome AF: 0.740

Gnomad NFE exome AF: 0.792

Gnomad OTH exome AF: 0.835

GnomAD4 exome AF: 0.796 AC: 1159462 AN: 1456336 Hom.: 464156 Cov.: 37 AF XY: 0.800 AC XY: 579713 AN XY: 724598

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.873

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.897

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.810

GnomAD4 genome AF: 0.779 AC: 118546 AN: 152126 Hom.: 46506 Cov.: 32 AF XY: 0.782 AC XY: 58168 AN XY: 74376

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.816

Alfa AF: 0.799 Hom.: 76110

Bravo AF: 0.786

TwinsUK AF: 0.774 AC: 2871

ALSPAC AF: 0.782 AC: 3015

ESP6500AA AF: 0.708 AC: 3120

ESP6500EA AF: 0.785 AC: 6750

ExAC AF: 0.825 AC: 100142

Asia WGS AF: 0.936 AC: 3256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.0
DANN	Benign	0.96
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.51	T;T
MetaRNN	Benign	8.4e-7	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.2e-13	P;P
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.061
Sift	Benign	0.32	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.040	B;.
Vest4		0.040
MPC		0.11
ClinPred		0.0042	T
GERP RS		1.1
Varity_R		0.049
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1129942; hg19: chr1-172437592; COSMIC: COSV62959312; COSMIC: COSV62959312;