rs7168069

Variant names:

• chr15-68332058-A-C
• rs7168069
• NM_001004439.2:c.1571T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-68332058-A-C
• chr15-68332058-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004439.2(ITGA11):​c.1571T>G​(p.Leu524Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,593,132 control chromosomes in the GnomAD database, including 560,427 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.86 (56025 hom., cov: 30)
  • Exomes 𝑓: 0.84 (504402 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 34 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1494022E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.1571T>G	p.Leu524Arg	missense_variant	Exon 14 of 30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.1364T>G	p.Leu455Arg	missense_variant	Exon 12 of 28		XP_011519665.1
ITGA11	XM_005254228.4	c.1265T>G	p.Leu422Arg	missense_variant	Exon 12 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.1571T>G	p.Leu524Arg	missense_variant	Exon 14 of 30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.1571T>G	p.Leu524Arg	missense_variant	Exon 14 of 30	2		ENSP00000403392.2
ITGA11	ENST00000566429.1	n.460T>G		non_coding_transcript_exon_variant	Exon 5 of 5	4
ITGA11	ENST00000569346.5	n.550T>G		non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130305 AN: 151938 Hom.: 55987 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.853

GnomAD2 exomes AF: 0.866 AC: 189692 AN: 219128 AF XY: 0.864

Gnomad AFR exome AF: 0.876

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.830

Gnomad EAS exome AF: 0.917

Gnomad FIN exome AF: 0.867

Gnomad NFE exome AF: 0.824

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.836 AC: 1204381 AN: 1441076 Hom.: 504402 Cov.: 43 AF XY: 0.838 AC XY: 598659 AN XY: 714524

African (AFR) AF: 0.877 AC: 29090 AN: 33166

American (AMR) AF: 0.926 AC: 38254 AN: 41296

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 21416 AN: 25804

East Asian (EAS) AF: 0.921 AC: 35853 AN: 38934

South Asian (SAS) AF: 0.919 AC: 76149 AN: 82842

European-Finnish (FIN) AF: 0.862 AC: 45152 AN: 52358

Middle Eastern (MID) AF: 0.881 AC: 5068 AN: 5750

European-Non Finnish (NFE) AF: 0.820 AC: 902943 AN: 1101190

Other (OTH) AF: 0.845 AC: 50456 AN: 59736

GnomAD4 genome AF: 0.858 AC: 130401 AN: 152056 Hom.: 56025 Cov.: 30 AF XY: 0.863 AC XY: 64122 AN XY: 74312

African (AFR) AF: 0.876 AC: 36327 AN: 41468

American (AMR) AF: 0.899 AC: 13749 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4721 AN: 5140

South Asian (SAS) AF: 0.925 AC: 4448 AN: 4808

European-Finnish (FIN) AF: 0.874 AC: 9258 AN: 10588

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56205 AN: 67974

Other (OTH) AF: 0.851 AC: 1796 AN: 2110

Alfa AF: 0.837 Hom.: 147967

Bravo AF: 0.860

TwinsUK AF: 0.811 AC: 3006

ALSPAC AF: 0.817 AC: 3148

ESP6500AA AF: 0.894 AC: 3491

ESP6500EA AF: 0.823 AC: 6830

ExAC AF: 0.855 AC: 102865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.13
DEOGEN2	Benign	0.066	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.022	T;T
MetaRNN	Benign	0.0000011	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N
PhyloP100		-0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.086
Sift	Benign	1.0	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	.;B
Vest4		0.042
MPC		0.16
ClinPred		0.00041	T
GERP RS		4.1
Varity_R		0.076
gMVP		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7168069; hg19: chr15-68624396; COSMIC: COSV107326968;