13-101453932-C-T

Variant names:

• chr13-101453932-C-T
• NM_004791.3:c.148C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004791.3(ITGBL1):​c.148C>T​(p.Arg50Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000806 in 1,240,946 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697

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 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.148C>T	p.Arg50Cys	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.148C>T	p.Arg50Cys	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1001C>T		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.148C>T	p.Arg50Cys	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.148C>T	p.Arg50Cys	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1001C>T		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.06e-7 AC: 1 AN: 1240946 Hom.: 0 Cov.: 33 AF XY: 0.00000165 AC XY: 1 AN XY: 607762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T;D
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.90	.;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	.;D
Vest4		0.62
MutPred		0.36		Gain of catalytic residue at G55 (P = 0.0018);Gain of catalytic residue at G55 (P = 0.0018);
MVP		0.57
MPC		0.88
ClinPred		0.96	D
GERP RS		0.42
Varity_R		0.33
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-102106283; COSMIC: COSV66021731;