Variant chr13-48233441-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_021999.5(ITM2B):c.81C>T(p.Leu27Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,540,578 control chromosomes in the GnomAD database, including 825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 250 hom., cov: 31)

Exomes 𝑓: 0.011 ( 575 hom. )

Consequence

ITM2B
NM_021999.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.638

Variant links:

Genes affected

ITM2B (HGNC:6174): (integral membrane protein 2B) Amyloid precursor proteins are processed by beta-secretase and gamma-secretase to produce beta-amyloid peptides which form the characteristic plaques of Alzheimer disease. This gene encodes a transmembrane protein which is processed at the C-terminus by furin or furin-like proteases to produce a small secreted peptide which inhibits the deposition of beta-amyloid. Mutations which result in extension of the C-terminal end of the encoded protein, thereby increasing the size of the secreted peptide, are associated with two neurogenerative diseases, familial British dementia and familial Danish dementia. [provided by RefSeq, Oct 2009]

ITM2B 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=-0.46).

BP6

Variant 13-48233441-C-T is Benign according to our data. Variant chr13-48233441-C-T is described in ClinVar as [Benign]. Clinvar id is 1210019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-48233441-C-T is described in Lovd as [Likely_benign]. Variant chr13-48233441-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.638 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITM2B	NM_021999.5 linkuse as main transcript	c.81C>T	p.Leu27Leu	synonymous_variant	1/6	ENST00000647800.2	NP_068839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITM2B	ENST00000647800.2 linkuse as main transcript	c.81C>T	p.Leu27Leu	synonymous_variant	1/6		NM_021999.5	ENSP00000497221.1		Q9Y287-1

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5205

AN:

151992

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0776

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0203

AC:

2959

AN:

145564

Hom.:

131

AF XY:

0.0221

AC XY:

1758

AN XY:

79602

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00678

Gnomad ASJ exome

AF:

0.000387

Gnomad EAS exome

AF:

0.0652

Gnomad SAS exome

AF:

0.0709

Gnomad FIN exome

AF:

0.000497

Gnomad NFE exome

AF:

0.00232

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0107

AC:

14904

AN:

1388478

Hom.:

575

Cov.:

AF XY:

0.0122

AC XY:

8358

AN XY:

686650

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.00741

Gnomad4 ASJ exome

AF:

0.000329

Gnomad4 EAS exome

AF:

0.0725

Gnomad4 SAS exome

AF:

0.0680

Gnomad4 FIN exome

AF:

0.000491

Gnomad4 NFE exome

AF:

0.00260

Gnomad4 OTH exome

AF:

0.0185

GnomAD4 genome

AF:

0.0344

AC:

5232

AN:

152100

Hom.:

250

Cov.:

AF XY:

0.0343

AC XY:

2553

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0615

Gnomad4 SAS

AF:

0.0775

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.0323

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0373

Asia WGS

AF:

0.122

AC:

420

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.8

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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