1-162379016-C-A

Variant names:

• chr1-162379016-C-A
• rs945797576
• ENST00000420220.1:c.-11-2875C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135240.4(C1orf226):​c.-27C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1orf226 NM_001135240.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

ENSG00000254706 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11469343).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135240.4. 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_001135240.4		c.-27C>A		5_prime_UTR	Exon 1 of 3	NP_001128712.2	A1L170-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000254706	ENST00000420220.1	TSL:5	c.-11-2875C>A		intron	N/A	ENSP00000398035.1	F8W6W0
	C1orf226	ENST00000426197.2	TSL:2	c.103C>A	p.Pro35Thr	missense	Exon 1 of 3	ENSP00000413150.2	A1L170-2
	ENSG00000254706	ENST00000431696.1	TSL:4	c.227-2875C>A		intron	N/A	ENSP00000405676.2	H7C2G1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396676 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 689106

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076660

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.86	T
PhyloP100		1.3
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.098	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.60	P
Vest4		0.25
MutPred		0.084		Gain of phosphorylation at P35 (P = 0.0762)
MVP		0.043
MPC		0.073
ClinPred		0.62	D
GERP RS		4.7
PromoterAI		0.0013	Neutral
gMVP		0.86
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs945797576; hg19: chr1-162348806;