Genetic Variant ITGBL1:p.Lys136Asn (chr13-101567790-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004791.3(ITGBL1):c.408G>T(p.Lys136Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Publications

0 publications found

Variant links:

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ITGBL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16117966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.408G>T	p.Lys136Asn	missense_variant	Exon 3 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271756.2 link	c.129G>T	p.Lys43Asn	missense_variant	Exon 2 of 10		NP_001258685.1	O95965-3
ITGBL1	NM_001271754.2 link	c.-16G>T		5_prime_UTR_variant	Exon 2 of 11		NP_001258683.1	O95965-2B4DN32
ITGBL1	NM_001271755.2 link	c.317-7634G>T		intron_variant	Intron 2 of 9		NP_001258684.1	O95965A0A087WY35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 link	c.408G>T	p.Lys136Asn	missense_variant	Exon 3 of 11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 link	c.317-7634G>T		intron_variant	Intron 2 of 9	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000376162.7 link	c.129G>T	p.Lys43Asn	missense_variant	Exon 2 of 10	2		ENSP00000365332.3	O95965-3
ITGBL1	ENST00000545560.6 link	c.-16G>T		5_prime_UTR_variant	Exon 2 of 11	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111498

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.408G>T (p.K136N) alteration is located in exon 3 (coding exon 3) of the ITGBL1 gene. This alteration results from a G to T substitution at nucleotide position 408, causing the lysine (K) at amino acid position 136 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

T;T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.70

T;T;T

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.2

L;.;.

PhyloP100

2.5

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.53

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.10

T;.;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.14

B;.;.

Vest4

0.32

MutPred

0.36

Loss of methylation at K136 (P = 0.0157);.;.;

MVP

0.58

MPC

0.25

ClinPred

0.43

GERP RS

4.3

Varity_R

0.061

gMVP

0.59

Mutation Taster

=83/17

polymorphism

(source)

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

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chr13-101567790-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over