1-1086035-A-G

Variant names:

• chr1-1086035-A-G
• rs3737728
• NM_017891.5:c.311-23T>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.311-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,610,786 control chromosomes in the GnomAD database, including 438,884 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 0.76 (43689 hom., cov: 36)
  • Exomes 𝑓: 0.73 (395195 hom.)
• Consequence: C1orf159 NM_017891.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 15 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	NM_017891.5	MANE Select	c.311-23T>C		intron	N/A	NP_060361.4
	C1orf159	NM_001330306.2		c.419-23T>C		intron	N/A	NP_001317235.1	Q96HA4-1
	C1orf159	NM_001363525.2		c.311-23T>C		intron	N/A	NP_001350454.1	Q5T2W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	ENST00000421241.7	TSL:2 MANE Select	c.311-23T>C		intron	N/A	ENSP00000400736.2	Q96HA4-4
	C1orf159	ENST00000379339.5	TSL:2	c.419-23T>C		intron	N/A	ENSP00000368644.1	Q96HA4-1
	C1orf159	ENST00000379320.5	TSL:2	c.311-23T>C		intron	N/A	ENSP00000368624.1	Q5T2W9

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114937 AN: 152172 Hom.: 43652 Cov.: 36

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.762 AC: 188000 AN: 246568 AF XY: 0.760

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.823

Gnomad ASJ exome AF: 0.797

Gnomad EAS exome AF: 0.895

Gnomad FIN exome AF: 0.730

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.756

GnomAD4 exome AF: 0.735 AC: 1071693 AN: 1458496 Hom.: 395195 Cov.: 51 AF XY: 0.736 AC XY: 533574 AN XY: 725396

African (AFR) AF: 0.780 AC: 26107 AN: 33450

American (AMR) AF: 0.821 AC: 36606 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 20798 AN: 26084

East Asian (EAS) AF: 0.910 AC: 36102 AN: 39662

South Asian (SAS) AF: 0.781 AC: 67252 AN: 86142

European-Finnish (FIN) AF: 0.729 AC: 37777 AN: 51824

Middle Eastern (MID) AF: 0.775 AC: 4325 AN: 5580

European-Non Finnish (NFE) AF: 0.718 AC: 797666 AN: 1110912

Other (OTH) AF: 0.748 AC: 45060 AN: 60258

GnomAD4 genome AF: 0.755 AC: 115038 AN: 152290 Hom.: 43689 Cov.: 36 AF XY: 0.759 AC XY: 56506 AN XY: 74462

African (AFR) AF: 0.784 AC: 32590 AN: 41552

American (AMR) AF: 0.795 AC: 12163 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2815 AN: 3470

East Asian (EAS) AF: 0.897 AC: 4645 AN: 5180

South Asian (SAS) AF: 0.781 AC: 3775 AN: 4834

European-Finnish (FIN) AF: 0.732 AC: 7774 AN: 10624

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48746 AN: 68006

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.730 Hom.: 61217

Bravo AF: 0.760

Asia WGS AF: 0.840 AC: 2922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.33
PhyloP100		-1.3
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: rs3737728; hg19: chr1-1021415; COSMIC: COSV53881166; COSMIC: COSV53881166;