rs759374278

Variant names:

• chr13-101453975-A-G
• rs759374278
• NM_004791.3:c.191A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004791.3(ITGBL1):​c.191A>G​(p.His64Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,530,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039764434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.191A>G	p.His64Arg	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.191A>G	p.His64Arg	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1044A>G		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.191A>G	p.His64Arg	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.191A>G	p.His64Arg	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1044A>G		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000360 AC: 5 AN: 138794 AF XY: 0.0000267

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000534

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000943 AC: 13 AN: 1378244 Hom.: 0 Cov.: 33 AF XY: 0.0000147 AC XY: 10 AN XY: 680422

African (AFR) AF: 0.00 AC: 0 AN: 29908

American (AMR) AF: 0.00 AC: 0 AN: 33882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24516

East Asian (EAS) AF: 0.000264 AC: 9 AN: 34042

South Asian (SAS) AF: 0.00 AC: 0 AN: 76372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068300

Other (OTH) AF: 0.0000703 AC: 4 AN: 56916

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000268 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.191A>G (p.H64R) alteration is located in exon 2 (coding exon 2) of the ITGBL1 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the histidine (H) at amino acid position 64 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.47	T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.040	T;T
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Benign	1.2	.;L
PhyloP100		3.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.52	.;N
REVEL	Uncertain	0.34
Sift	Benign	0.038	.;D
Sift4G	Benign	0.33	T;T
Polyphen		0.41	.;B
Vest4		0.43
MutPred		0.63		Gain of catalytic residue at A60 (P = 0.0057);Gain of catalytic residue at A60 (P = 0.0057);
MVP		0.64
MPC		0.29
ClinPred		0.085	T
GERP RS		5.8
Varity_R		0.12
gMVP		0.54
Mutation Taster		=88/12	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: rs759374278; hg19: chr13-102106326;