rs200676589

Variant names:

• chr1-230843535-C-T
• rs200676589
• NM_032800.3:c.746G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-230843535-C-T
• chr1-230843535-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032800.3(C1orf198):​c.746G>A​(p.Arg249His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,612,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: C1orf198 NM_032800.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.570
• Publications: 0 publications found

Genes affected

C1orf198 (HGNC:25900): (chromosome 1 open reading frame 198) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042651713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032800.3. 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
	C1orf198	NM_032800.3	MANE Select	c.746G>A	p.Arg249His	missense	Exon 3 of 4	NP_116189.1	Q9H425-1
	C1orf198	NM_001136494.2		c.632G>A	p.Arg211His	missense	Exon 5 of 6	NP_001129966.1	Q9H425-3
	C1orf198	NM_001136495.2		c.356G>A	p.Arg119His	missense	Exon 3 of 4	NP_001129967.1	Q9H425-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf198	ENST00000366663.10	TSL:1 MANE Select	c.746G>A	p.Arg249His	missense	Exon 3 of 4	ENSP00000355623.5	Q9H425-1
	C1orf198	ENST00000470540.5	TSL:2	c.632G>A	p.Arg211His	missense	Exon 5 of 6	ENSP00000428172.1	Q9H425-3
	C1orf198	ENST00000523410.1	TSL:2	c.356G>A	p.Arg119His	missense	Exon 3 of 4	ENSP00000430967.1	Q9H425-2

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000212 AC: 53 AN: 249744 AF XY: 0.000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000346 AC: 505 AN: 1459932 Hom.: 0 Cov.: 31 AF XY: 0.000306 AC XY: 222 AN XY: 726030

African (AFR) AF: 0.0000299 AC: 1 AN: 33442

American (AMR) AF: 0.000314 AC: 14 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86124

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53358

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.000395 AC: 439 AN: 1110746

Other (OTH) AF: 0.000747 AC: 45 AN: 60276

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74368

African (AFR) AF: 0.000145 AC: 6 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000344 Hom.: 0

Bravo AF: 0.000234

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.57
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.013
Sift	Benign	0.072	T
Sift4G	Benign	0.22	T
Polyphen		0.010	B
Vest4		0.11
MVP		0.25
MPC		0.70
ClinPred		0.066	T
GERP RS		2.5
Varity_R		0.021
gMVP		0.093
Mutation Taster		=95/5	polymorphism

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: rs200676589; hg19: chr1-230979281;