rs11806859

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

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

ENSG00000254706 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but rather VUS (scored 4 / 10). 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf226	NM_001085375.2	c.318-31G>A		intron_variant		ENST00000458626.4	NP_001078844.1
C1orf226	NM_001135240.3	c.447-31G>A		intron_variant			NP_001128712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf226	ENST00000458626.4	c.318-31G>A		intron_variant		1	NM_001085375.2	ENSP00000437071.1
ENSG00000254706	ENST00000420220.1	c.318-31G>A		intron_variant		5		ENSP00000398035.1
C1orf226	ENST00000426197.2	c.447-31G>A		intron_variant		2		ENSP00000413150.2
ENSG00000254706	ENST00000367932.3	n.*325-31G>A		intron_variant		4		ENSP00000356909.3

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

GnomAD3 exomes AF: 0.255 AC: 46796 AN: 183220 Hom.: 6318 AF XY: 0.263 AC XY: 25466 AN XY: 96970

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 SAS exome AF: 0.337

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

Gnomad4 AFR exome AF: 0.0872

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.264

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

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.221

Alfa AF: 0.248 Hom.: 1912

Bravo AF: 0.215

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.77
DANN	Benign	0.66
BranchPoint Hunter		4.0

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: rs11806859; hg19: chr1-162352941; COSMIC: COSV63396579; COSMIC: COSV63396579;