13-101567790-G-T

Position:

• chr13-101567790-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004791.3(ITGBL1):​c.408G>T​(p.Lys136Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16117966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.408G>T	p.Lys136Asn	missense_variant	3/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271756.2	c.129G>T	p.Lys43Asn	missense_variant	2/10		NP_001258685.1
ITGBL1	NM_001271754.2	c.-16G>T		5_prime_UTR_variant	2/11		NP_001258683.1
ITGBL1	NM_001271755.2	c.317-7634G>T		intron_variant			NP_001258684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.408G>T	p.Lys136Asn	missense_variant	3/11	1	NM_004791.3	ENSP00000365351	P1
ITGBL1	ENST00000618057.4	c.317-7634G>T		intron_variant		1		ENSP00000481484
ITGBL1	ENST00000376162.7	c.129G>T	p.Lys43Asn	missense_variant	2/10	2		ENSP00000365332
ITGBL1	ENST00000545560.6	c.-16G>T		5_prime_UTR_variant	2/11	2		ENSP00000439903

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461084 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726856

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.408G>T (p.K136N) alteration is located in exon 3 (coding exon 3) of the ITGBL1 gene. This alteration results from a G to T substitution at nucleotide position 408, causing the lysine (K) at amino acid position 136 to be replaced by an asparagine (N). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T;T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.53	N;.;N
REVEL	Benign	0.13
Sift	Benign	0.10	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.14	B;.;.
Vest4		0.32
MutPred		0.36		Loss of methylation at K136 (P = 0.0157);.;.;
MVP		0.58
MPC		0.25
ClinPred		0.43	T
GERP RS		4.3
Varity_R		0.061
gMVP		0.59

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: rs2050205620; hg19: chr13-102220141;