NM_004791.3:c.94C>G

Variant names:

• chr13-101452927-C-G
• NM_004791.3:c.94C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004791.3(ITGBL1):​c.94C>G​(p.Leu32Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• Publications: 0 publications found

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

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=0.34818366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271754.2	c.-112C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11		NP_001258683.1
ITGBL1	NM_001271755.2	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-112C>G		5_prime_UTR_variant	Exon 1 of 11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-112C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	2		ENSP00000439903.1
ITGBL1	ENST00000545560.6	c.-112C>G		5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94C>G (p.L32V) alteration is located in exon 1 (coding exon 1) of the ITGBL1 gene. This alteration results from a C to G substitution at nucleotide position 94, causing the leucine (L) at amino acid position 32 to be replaced by a valine (V). 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	Benign	0.086
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0099	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.6	.;L
PhyloP100		3.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.47	.;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.027	.;D
Sift4G	Benign	0.13	T;T
Polyphen		1.0	.;D
Vest4		0.43
MutPred		0.42		Gain of catalytic residue at L32 (P = 0.0327);Gain of catalytic residue at L32 (P = 0.0327);
MVP		0.79
MPC		0.33
ClinPred		0.96	D
GERP RS		5.5
PromoterAI		-0.066	Neutral
Varity_R		0.17
gMVP		0.45
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

hg19: chr13-102105278;