chr13-101453981-G-C

Variant names:

• chr13-101453981-G-C
• NM_004791.3:c.197G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004791.3(ITGBL1):​c.197G>C​(p.Arg66Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,385,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.197G>C	p.Arg66Pro	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.197G>C	p.Arg66Pro	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1050G>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.197G>C	p.Arg66Pro	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.197G>C	p.Arg66Pro	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1050G>C		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1385912 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 684370

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: 0.00000186

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	0.91
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.8	.;H
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.052	T;D
Polyphen		1.0	.;D
Vest4		0.80
MutPred		0.60		Gain of catalytic residue at D70 (P = 0);Gain of catalytic residue at D70 (P = 0);
MVP		0.67
MPC		0.84
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.66
gMVP		0.82

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: chr13-102106332;