NM_004791.3:c.445A>T

Variant names:

• chr13-101567827-A-T
• rs766447430
• NM_004791.3:c.445A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004791.3(ITGBL1):​c.445A>T​(p.Ile149Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.411
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06900972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.445A>T	p.Ile149Phe	missense_variant	Exon 3 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271756.2	c.166A>T	p.Ile56Phe	missense_variant	Exon 2 of 10		NP_001258685.1
ITGBL1	NM_001271754.2	c.22A>T	p.Ile8Phe	missense_variant	Exon 2 of 11		NP_001258683.1
ITGBL1	NM_001271755.2	c.317-7597A>T		intron_variant	Intron 2 of 9		NP_001258684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.445A>T	p.Ile149Phe	missense_variant	Exon 3 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.317-7597A>T		intron_variant	Intron 2 of 9	1		ENSP00000481484.1
ITGBL1	ENST00000376162.7	c.166A>T	p.Ile56Phe	missense_variant	Exon 2 of 10	2		ENSP00000365332.3
ITGBL1	ENST00000545560.6	c.22A>T	p.Ile8Phe	missense_variant	Exon 2 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 11 AN: 250792 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1460882 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 726754

African (AFR) AF: 0.0000898 AC: 3 AN: 33396

American (AMR) AF: 0.0000896 AC: 4 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111388

Other (OTH) AF: 0.0000663 AC: 4 AN: 60324

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74344

African (AFR) AF: 0.000265 AC: 11 AN: 41458

American (AMR) AF: 0.000328 AC: 5 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445A>T (p.I149F) alteration is located in exon 3 (coding exon 3) of the ITGBL1 gene. This alteration results from a A to T substitution at nucleotide position 445, causing the isoleucine (I) at amino acid position 149 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.64
DEOGEN2	Benign	0.018	T;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.82	T;D;T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PhyloP100		0.41
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.23	N;.;N;N
REVEL	Benign	0.21
Sift	Benign	0.061	T;.;D;D
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.025	B;.;.;.
Vest4		0.29
MVP		0.26
MPC		0.32
ClinPred		0.032	T
GERP RS		-5.2
Varity_R		0.061
gMVP		0.64
Mutation Taster		=82/18	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: rs766447430; hg19: chr13-102220178;