NM_004791.3:c.821G>C

Variant names:

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

Variant summary

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

The NM_004791.3(ITGBL1):​c.821G>C​(p.Arg274Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,822 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: 𝑓 0.0000066 (0 hom., cov: 31)
• 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>C	p.Arg274Thr	missense_variant	Exon 6 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.674G>C	p.Arg225Thr	missense_variant	Exon 5 of 10		NP_001258684.1
ITGBL1	NM_001271756.2	c.542G>C	p.Arg181Thr	missense_variant	Exon 5 of 10		NP_001258685.1
ITGBL1	NM_001271754.2	c.398G>C	p.Arg133Thr	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>C	p.Arg274Thr	missense_variant	Exon 6 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.674G>C	p.Arg225Thr	missense_variant	Exon 5 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000376162.7	c.542G>C	p.Arg181Thr	missense_variant	Exon 5 of 10	2		ENSP00000365332.3
ITGBL1	ENST00000545560.6	c.398G>C	p.Arg133Thr	missense_variant	Exon 5 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151822 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151822 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74114

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.0096	T;T;T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.72	.;N;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.090	.;N;.;N;D
REVEL	Pathogenic	0.65
Sift	Benign	0.18	.;T;.;D;D
Sift4G	Benign	0.45	T;T;T;T;T
Polyphen		0.42	.;B;.;.;.
Vest4		0.67
MutPred		0.45		.;Gain of catalytic residue at E273 (P = 0.0121);.;.;.;
MVP		0.62
MPC		0.87
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.55

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;