rs7545952

Positions:

• chr1-1095680-A-G
• chr1-1095680-A-T

Variant summary

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

The NM_017891.5(C1orf159):​c.-135-3577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,180 control chromosomes in the GnomAD database, including 778 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 0.093 (778 hom., cov: 33)
• Consequence: C1orf159 NM_017891.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf159	NM_017891.5	c.-135-3577T>C		intron_variant		ENST00000421241.7
C1orf159	NM_001330306.2	c.-135-3577T>C		intron_variant
C1orf159	NM_001363525.2	c.-135-3577T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf159	ENST00000421241.7	c.-135-3577T>C		intron_variant		2	NM_017891.5	P1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14116 AN: 152062 Hom.: 776 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0929 AC: 14138 AN: 152180 Hom.: 778 Cov.: 33 AF XY: 0.0957 AC XY: 7122 AN XY: 74402

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0555

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0811 Hom.: 56

Bravo AF: 0.0943

Asia WGS AF: 0.132 AC: 458 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.75

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: rs7545952; hg19: chr1-1031060;