Genetic Variant NM_004791.3:c.157G>T (chr13-101453941-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004791.3(ITGBL1):c.157G>T(p.Ala53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,418,364 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A53P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37830728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.157G>T	p.Ala53Ser	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271755.2 link	c.157G>T	p.Ala53Ser	missense_variant	Exon 2 of 10		NP_001258684.1	O95965A0A087WY35
ITGBL1	NM_001271754.2 link	c.-108+1010G>T		intron_variant	Intron 1 of 10		NP_001258683.1	O95965-2B4DN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 link	c.157G>T	p.Ala53Ser	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 link	c.157G>T	p.Ala53Ser	missense_variant	Exon 2 of 10	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000545560.6 link	c.-108+1010G>T		intron_variant	Intron 1 of 10	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000158

AC:

AN:

1266276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

622046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25708

American (AMR)

AF:

0.00

AC:

AN:

21084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20484

East Asian (EAS)

AF:

0.00

AC:

AN:

28074

South Asian (SAS)

AF:

0.00

AC:

AN:

60150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4604

European-Non Finnish (NFE)

AF:

0.00000198

AC:

AN:

1011310

Other (OTH)

AF:

0.00

AC:

AN:

51266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.85

.;L

PhyloP100

4.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.36

.;N

REVEL

Uncertain

0.31

Sift

Benign

0.16

.;T

Sift4G

Benign

0.46

T;T

Polyphen

0.87

.;P

Vest4

0.36

MutPred

0.27

Gain of catalytic residue at P57 (P = 0);Gain of catalytic residue at P57 (P = 0);

MVP

0.72

MPC

0.23

ClinPred

0.68

GERP RS

5.4

Varity_R

0.15

gMVP

0.16

Mutation Taster

=88/12

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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NM_004791.3:c.157G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over