rs11806859

Variant names:

• chr1-162383151-G-A
• rs11806859
• NM_001085375.2:c.318-31G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162383151-G-A
• chr1-162383151-G-C

Variant summary

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

The NM_001085375.2(C1orf226):​c.318-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,524,234 control chromosomes in the GnomAD database, including 58,896 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.22 (4412 hom., cov: 33)
  • Exomes 𝑓: 0.28 (54484 hom.)
• Consequence: C1orf226 NM_001085375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 14 publications found

Genes affected

C1orf226 (HGNC:34351): (chromosome 1 open reading frame 226)

ENSG00000254706 (HGNC:):

ACMG classification

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085375.2. 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
	C1orf226	NM_001085375.2	MANE Select	c.318-31G>A		intron	N/A	NP_001078844.1	A1L170-1
	C1orf226	NM_001135240.4		c.318-31G>A		intron	N/A	NP_001128712.2	A1L170-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf226	ENST00000458626.4	TSL:1 MANE Select	c.318-31G>A		intron	N/A	ENSP00000437071.1	A1L170-1
	ENSG00000254706	ENST00000420220.1	TSL:5	c.318-31G>A		intron	N/A	ENSP00000398035.1	F8W6W0
	C1orf226	ENST00000426197.2	TSL:2	c.447-31G>A		intron	N/A	ENSP00000413150.2	A1L170-2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34150 AN: 152066 Hom.: 4412 Cov.: 33

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.255 AC: 46796 AN: 183220 AF XY: 0.263

Gnomad AFR exome AF: 0.0926

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.278 AC: 381145 AN: 1372050 Hom.: 54484 Cov.: 31 AF XY: 0.280 AC XY: 188443 AN XY: 672538

African (AFR) AF: 0.0872 AC: 2682 AN: 30764

American (AMR) AF: 0.219 AC: 6971 AN: 31820

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 5299 AN: 20484

East Asian (EAS) AF: 0.203 AC: 7874 AN: 38830

South Asian (SAS) AF: 0.344 AC: 24560 AN: 71402

European-Finnish (FIN) AF: 0.262 AC: 13146 AN: 50214

Middle Eastern (MID) AF: 0.237 AC: 1264 AN: 5338

European-Non Finnish (NFE) AF: 0.285 AC: 304442 AN: 1066720

Other (OTH) AF: 0.264 AC: 14907 AN: 56478

GnomAD4 genome AF: 0.224 AC: 34150 AN: 152184 Hom.: 4412 Cov.: 33 AF XY: 0.224 AC XY: 16656 AN XY: 74402

African (AFR) AF: 0.0997 AC: 4143 AN: 41536

American (AMR) AF: 0.239 AC: 3651 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1056 AN: 5166

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2623 AN: 10582

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19370 AN: 67984

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.246 Hom.: 1919

Bravo AF: 0.215

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.77
DANN	Benign	0.66
PhyloP100		1.6
BranchPoint Hunter		4.0
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: rs11806859; hg19: chr1-162352941; COSMIC: COSV63396579; COSMIC: COSV63396579;