Variant 1-6232010-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012405.4(ICMT):c.564G>A(p.Val188Val) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

ICMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

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	Protein	UniProt
ICMT	NM_012405.4 linkuse as main transcript	c.564G>A	p.Val188Val	synonymous_variant	4/5	ENST00000343813.10	NP_036537.1	O60725A0A024R4F6
ICMT	XM_011541140.3 linkuse as main transcript	c.276G>A	p.Val92Val	synonymous_variant	3/4		XP_011539442.1	B3KS61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICMT	ENST00000343813.10 linkuse as main transcript	c.564G>A	p.Val188Val	synonymous_variant	4/5	1	NM_012405.4	ENSP00000343552.5		O60725

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3252

AN:

152092

Hom.:

111

Cov.:

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.:

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.:

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

AF:

0.0214

AC:

3261

AN:

152210

Hom.:

110

Cov.:

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.:

Bravo

AF:

0.0247

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over