1-1094425-A-G

Position:

• chr1-1094425-A-G

Variant summary

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

The NM_017891.5(C1orf159):​c.-135-2322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 148,754 control chromosomes in the GnomAD database, including 7,646 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 0.28 (7646 hom., cov: 31)
• Consequence: C1orf159 NM_017891.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf159	NM_017891.5	c.-135-2322T>C		intron_variant		ENST00000421241.7	NP_060361.4
C1orf159	NM_001330306.2	c.-135-2322T>C		intron_variant			NP_001317235.1
C1orf159	NM_001363525.2	c.-135-2322T>C		intron_variant			NP_001350454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf159	ENST00000421241.7	c.-135-2322T>C		intron_variant		2	NM_017891.5	ENSP00000400736	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 41763 AN: 148632 Hom.: 7637 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.281 AC: 41812 AN: 148754 Hom.: 7646 Cov.: 31 AF XY: 0.282 AC XY: 20406 AN XY: 72364

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.268

Alfa AF: 0.222 Hom.: 808

Bravo AF: 0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.23

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

Other links and lift over

dbSNP: rs6689308; hg19: chr1-1029805;