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GeneBe

1-6232010-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_012405.4(ICMT):c.564G>A(p.Val188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,614,058 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 110 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 114 hom. )

Consequence

ICMT
NM_012405.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-6232010-C-T is Benign according to our data. Variant chr1-6232010-C-T is described in ClinVar as [Benign]. Clinvar id is 775494.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ICMTNM_012405.4 linkuse as main transcriptc.564G>A p.Val188= synonymous_variant 4/5 ENST00000343813.10
ICMTXM_011541140.3 linkuse as main transcriptc.276G>A p.Val92= synonymous_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ICMTENST00000343813.10 linkuse as main transcriptc.564G>A p.Val188= synonymous_variant 4/51 NM_012405.4 P1
ICMTENST00000489498.5 linkuse as main transcriptc.*320G>A 3_prime_UTR_variant, NMD_transcript_variant 5/61
ICMTENST00000474756.1 linkuse as main transcriptc.*109G>A 3_prime_UTR_variant, NMD_transcript_variant 3/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0214
AC:
3252
AN:
152092
Hom.:
111
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0735
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00930
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.0230
GnomAD3 exomes
AF:
0.00577
AC:
1450
AN:
251432
Hom.:
50
AF XY:
0.00420
AC XY:
571
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0783
Gnomad AMR exome
AF:
0.00298
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000220
Gnomad OTH exome
AF:
0.00391
GnomAD4 exome
AF:
0.00225
AC:
3291
AN:
1461848
Hom.:
114
Cov.:
32
AF XY:
0.00199
AC XY:
1449
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0771
Gnomad4 AMR exome
AF:
0.00402
Gnomad4 ASJ exome
AF:
0.00168
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000125
Gnomad4 OTH exome
AF:
0.00510
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0214
AC:
3261
AN:
152210
Hom.:
110
Cov.:
33
AF XY:
0.0215
AC XY:
1603
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0735
Gnomad4 AMR
AF:
0.00929
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.0137
Hom.:
32
Bravo
AF:
0.0247
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
12
Dann
Benign
0.82

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35465282; hg19: chr1-6292070; API