13-101583231-G-A

Position:

• chr13-101583231-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004791.3(ITGBL1):​c.743G>A​(p.Gly248Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.743G>A	p.Gly248Asp	missense_variant	6/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.596G>A	p.Gly199Asp	missense_variant	5/10		NP_001258684.1
ITGBL1	NM_001271756.2	c.464G>A	p.Gly155Asp	missense_variant	5/10		NP_001258685.1
ITGBL1	NM_001271754.2	c.320G>A	p.Gly107Asp	missense_variant	5/11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.743G>A	p.Gly248Asp	missense_variant	6/11	1	NM_004791.3	ENSP00000365351	P1
ITGBL1	ENST00000618057.4	c.596G>A	p.Gly199Asp	missense_variant	5/10	1		ENSP00000481484
ITGBL1	ENST00000376162.7	c.464G>A	p.Gly155Asp	missense_variant	5/10	2		ENSP00000365332
ITGBL1	ENST00000545560.6	c.320G>A	p.Gly107Asp	missense_variant	5/11	2		ENSP00000439903

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.743G>A (p.G248D) alteration is located in exon 6 (coding exon 6) of the ITGBL1 gene. This alteration results from a G to A substitution at nucleotide position 743, causing the glycine (G) at amino acid position 248 to be replaced by an aspartic acid (D). 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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T;.;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Pathogenic	0.51	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.2	.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	.;N;.;D;D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0050	.;D;.;D;D
Sift4G	Benign	0.10	T;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.92
MutPred		0.37		.;Gain of catalytic residue at E249 (P = 0);.;.;.;
MVP		0.88
MPC		0.87
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.51
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-102235581;