chr1-6233332-T-C

Variant names:

• chr1-6233332-T-C
• rs846108
• NM_012405.4:c.454+142A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_012405.4(ICMT):​c.454+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 731,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: ICMT NM_012405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 1 publications found

Genes affected

ICMT (HGNC:5350): (isoprenylcysteine carboxyl methyltransferase) This gene encodes the third of three enzymes that posttranslationally modify isoprenylated C-terminal cysteine residues in certain proteins and target those proteins to the cell membrane. This enzyme localizes to the endoplasmic reticulum. Alternative splicing may result in other transcript variants, but the biological validity of those transcripts has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012405.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICMT	NM_012405.4	MANE Select	c.454+142A>G		intron	N/A	NP_036537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICMT	ENST00000343813.10	TSL:1 MANE Select	c.454+142A>G		intron	N/A	ENSP00000343552.5
	ICMT	ENST00000489498.5	TSL:1	n.*210+142A>G		intron	N/A	ENSP00000466222.1
	ICMT	ENST00000474756.1	TSL:2	n.285-1213A>G		intron	N/A	ENSP00000467999.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152262 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000301 AC: 174 AN: 578866 Hom.: 0 AF XY: 0.000276 AC XY: 84 AN XY: 303912

African (AFR) AF: 0.00 AC: 0 AN: 15652

American (AMR) AF: 0.00 AC: 0 AN: 23608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14568

East Asian (EAS) AF: 0.00 AC: 0 AN: 34490

South Asian (SAS) AF: 0.00 AC: 0 AN: 46008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2242

European-Non Finnish (NFE) AF: 0.000456 AC: 171 AN: 375246

Other (OTH) AF: 0.0000999 AC: 3 AN: 30044

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152380 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74518

African (AFR) AF: 0.0000481 AC: 2 AN: 41596

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000378 Hom.: 0

Bravo AF: 0.000125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		0.55

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: rs846108; hg19: chr1-6293392;