chr1-1113575-A-G

Variant names:

• chr1-1113575-A-G
• rs4970405
• NM_017891.5:c.-136+2485T>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+2485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 152,208 control chromosomes in the GnomAD database, including 720 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 0.085 (720 hom., cov: 32)
• Consequence: C1orf159 NM_017891.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 4 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 (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017891.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	NM_017891.5	MANE Select	c.-136+2485T>C		intron	N/A	NP_060361.4
	C1orf159	NM_001330306.2		c.-136+1447T>C		intron	N/A	NP_001317235.1
	C1orf159	NM_001363525.2		c.-136+1447T>C		intron	N/A	NP_001350454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	ENST00000421241.7	TSL:2 MANE Select	c.-136+2485T>C		intron	N/A	ENSP00000400736.2
	C1orf159	ENST00000379339.5	TSL:2	c.-136+1447T>C		intron	N/A	ENSP00000368644.1
	C1orf159	ENST00000434641.5	TSL:5	c.-136+2485T>C		intron	N/A	ENSP00000390635.1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12926 AN: 152090 Hom.: 722 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0849 AC: 12916 AN: 152208 Hom.: 720 Cov.: 32 AF XY: 0.0836 AC XY: 6221 AN XY: 74418

African (AFR) AF: 0.0223 AC: 926 AN: 41548

American (AMR) AF: 0.114 AC: 1747 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3468

East Asian (EAS) AF: 0.173 AC: 895 AN: 5164

South Asian (SAS) AF: 0.173 AC: 836 AN: 4820

European-Finnish (FIN) AF: 0.0435 AC: 462 AN: 10614

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7084 AN: 67992

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.0958 Hom.: 456

Bravo AF: 0.0881

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.30
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: rs4970405; hg19: chr1-1048955;