1-172468452-G-A

Variant names:

• chr1-172468452-G-A
• rs1129942
• NM_139240.4:c.410G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 27 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf105	NM_139240.4	MANE Select	c.410G>A	p.Ser137Asn	missense	Exon 7 of 7	NP_640333.3
	C1orf105	NM_001300760.1		c.380G>A	p.Ser127Asn	missense	Exon 5 of 5	NP_001287689.1	Q5R3C7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.410G>A	p.Ser137Asn	missense	Exon 7 of 7	ENSP00000356700.4	O95561
	C1orf105	ENST00000367725.4	TSL:2	c.380G>A	p.Ser127Asn	missense	Exon 5 of 5	ENSP00000356698.4	Q5R3C7
	C1orf105	ENST00000367726.1	TSL:3	n.214G>A		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes AF: 0.827 AC: 206356 AN: 249618 AF XY: 0.830

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 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

African (AFR) AF: 0.701 AC: 23332 AN: 33282

American (AMR) AF: 0.873 AC: 38650 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 23056 AN: 25892

East Asian (EAS) AF: 0.999 AC: 39635 AN: 39668

South Asian (SAS) AF: 0.897 AC: 76905 AN: 85706

European-Finnish (FIN) AF: 0.740 AC: 39434 AN: 53272

Middle Eastern (MID) AF: 0.888 AC: 5093 AN: 5736

European-Non Finnish (NFE) AF: 0.780 AC: 864638 AN: 1108360

Other (OTH) AF: 0.810 AC: 48719 AN: 60156

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

African (AFR) AF: 0.703 AC: 29139 AN: 41472

American (AMR) AF: 0.848 AC: 12966 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3110 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5178 AN: 5186

South Asian (SAS) AF: 0.909 AC: 4381 AN: 4818

European-Finnish (FIN) AF: 0.732 AC: 7739 AN: 10572

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53297 AN: 68000

Other (OTH) AF: 0.816 AC: 1723 AN: 2112

Alfa AF: 0.794 Hom.: 118893

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 v4.9

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
MetaRNN	Benign	8.4e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.31
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.061
Sift	Benign	0.32	T
Sift4G	Benign	0.21	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1129942; hg19: chr1-172437592; COSMIC: COSV62959312; COSMIC: COSV62959312;