Genetic Variant ITGA11:p.Leu524Gln (chr15-68332058-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004439.2(ITGA11):c.1571T>A(p.Leu524Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,593,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L524R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

ITGA11
NM_001004439.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

Variant links:

Genes affected

ITGA11 (HGNC:6136): (integrin subunit alpha 11) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein contains an I domain, is expressed in muscle tissue, dimerizes with beta 1 integrin in vitro, and appears to bind collagen in this form. Therefore, the protein may be involved in attaching muscle tissue to the extracellular matrix. Alternative transcriptional splice variants have been found for this gene, but their biological validity is not determined. [provided by RefSeq, Jul 2008]

ITGA11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017698377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2 link	c.1571T>A	p.Leu524Gln	missense_variant	Exon 14 of 30	ENST00000315757.9	NP_001004439.1	Q9UKX5-1B3KTN6
ITGA11	XM_011521363.3 link	c.1364T>A	p.Leu455Gln	missense_variant	Exon 12 of 28		XP_011519665.1
ITGA11	XM_005254228.4 link	c.1265T>A	p.Leu422Gln	missense_variant	Exon 12 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGA11	ENST00000315757.9 link	c.1571T>A	p.Leu524Gln	missense_variant	Exon 14 of 30	1	NM_001004439.2	ENSP00000327290.7	Q9UKX5-1
ITGA11	ENST00000423218.6 link	c.1571T>A	p.Leu524Gln	missense_variant	Exon 14 of 30	2		ENSP00000403392.2	Q9UKX5-2
ITGA11	ENST00000566429.1 link	n.460T>A		non_coding_transcript_exon_variant	Exon 5 of 5	4
ITGA11	ENST00000569346.5 link	n.550T>A		non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000970

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

GnomAD3 exomes

AF:

0.0000548

AC:

AN:

219128

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

117620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000702

Gnomad SAS exome

AF:

0.0000372

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000902

AC:

AN:

1441860

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

714916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000231

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000973

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000997

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.33

DEOGEN2

Benign

0.091

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.035

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.33

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.42

N;N

REVEL

Benign

0.087

Sift

Benign

0.37

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0

.;B

Vest4

0.095

MutPred

0.52

Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);

MVP

0.38

MPC

0.11

ClinPred

0.023

GERP RS

4.1

Varity_R

0.078

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over