13-101453978-G-C

Variant names:

• chr13-101453978-G-C
• rs775199348
• NM_004791.3:c.194G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004791.3(ITGBL1):​c.194G>C​(p.Gly65Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G65D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.194G>C	p.Gly65Ala	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.194G>C	p.Gly65Ala	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1047G>C		intron_variant	Intron 1 of 10		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.194G>C	p.Gly65Ala	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.194G>C	p.Gly65Ala	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1047G>C		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.5	.;M
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.022	.;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.97	.;D
Vest4		0.49
MutPred		0.55		Gain of catalytic residue at D70 (P = 0);Gain of catalytic residue at D70 (P = 0);
MVP		0.76
MPC		0.48
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.68
Mutation Taster		=82/18	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

dbSNP: rs775199348; hg19: chr13-102106329;