dbSNP rs752269800: ITGBL1:p.Pro3Thr (chr13-101452840-C-A) – 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.7C>A(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. P3S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

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=0.12979499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271755.2 link	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 10		NP_001258684.1	O95965A0A087WY35
ITGBL1	NM_001271754.2 link	c.-199C>A		5_prime_UTR_variant	Exon 1 of 11		NP_001258683.1	O95965-2B4DN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 link	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 link	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 10	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000545560.6 link	c.-199C>A		5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461254

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111494

Other (OTH)

AF:

0.00

AC:

AN:

60364

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

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.4

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0095

T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.71

.;N

PhyloP100

0.12

PrimateAI

Benign

0.39

PROVEAN

Benign

0.49

.;N

REVEL

Benign

0.17

Sift

Benign

0.11

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

.;B

Vest4

0.17

MutPred

0.33

Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);

MVP

0.42

MPC

0.22

ClinPred

0.11

GERP RS

3.6

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.042

gMVP

0.55

Mutation Taster

=80/20

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over