NM_004791.3:c.821G>T

Variant names:

• chr13-101583309-G-T
• rs750974072
• NM_004791.3:c.821G>T

Variant summary

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

The NM_004791.3(ITGBL1):​c.821G>T​(p.Arg274Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,832 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: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

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.821G>T	p.Arg274Met	missense_variant	Exon 6 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.674G>T	p.Arg225Met	missense_variant	Exon 5 of 10		NP_001258684.1
ITGBL1	NM_001271756.2	c.542G>T	p.Arg181Met	missense_variant	Exon 5 of 10		NP_001258685.1
ITGBL1	NM_001271754.2	c.398G>T	p.Arg133Met	missense_variant	Exon 5 of 11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.821G>T	p.Arg274Met	missense_variant	Exon 6 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.674G>T	p.Arg225Met	missense_variant	Exon 5 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000376162.7	c.542G>T	p.Arg181Met	missense_variant	Exon 5 of 10	2		ENSP00000365332.3
ITGBL1	ENST00000545560.6	c.398G>T	p.Arg133Met	missense_variant	Exon 5 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250058 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460832 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726746

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T;T;T;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.0	.;L;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.23	.;N;.;N;D
REVEL	Uncertain	0.61
Sift	Benign	0.061	.;T;.;D;D
Sift4G	Benign	0.085	T;T;T;D;T
Polyphen		1.0	.;D;.;.;.
Vest4		0.65
MutPred		0.49		.;Gain of catalytic residue at R274 (P = 0);.;.;.;
MVP		0.69
MPC		0.80
ClinPred		0.78	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs750974072; hg19: chr13-102235659;