chr1-1114570-A-G

Variant names:

• chr1-1114570-A-G
• rs12726255
• NM_017891.5:c.-136+1490T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017891.5(C1orf159):​c.-136+1490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 6,495 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 0.25 (6495 hom., cov: 32)
• Consequence: C1orf159 NM_017891.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 10 publications found

Genes affected

C1orf159 (HGNC:26062): (chromosome 1 open reading frame 159) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf159	NM_017891.5	c.-136+1490T>C		intron_variant	Intron 1 of 9	ENST00000421241.7	NP_060361.4
C1orf159	NM_001330306.2	c.-136+452T>C		intron_variant	Intron 2 of 11		NP_001317235.1
C1orf159	NM_001363525.2	c.-136+452T>C		intron_variant	Intron 2 of 10		NP_001350454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf159	ENST00000421241.7	c.-136+1490T>C		intron_variant	Intron 1 of 9	2	NM_017891.5	ENSP00000400736.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37712 AN: 151956 Hom.: 6480 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.251

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37772 AN: 152074 Hom.: 6495 Cov.: 32 AF XY: 0.243 AC XY: 18088 AN XY: 74346

African (AFR) AF: 0.494 AC: 20489 AN: 41440

American (AMR) AF: 0.196 AC: 2999 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1084 AN: 5172

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1138 AN: 10606

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9588 AN: 67958

Other (OTH) AF: 0.249 AC: 526 AN: 2112

Alfa AF: 0.173 Hom.: 1536

Bravo AF: 0.267

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.47
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12726255; hg19: chr1-1049950;