rs2306022

Variant names:

• chr15-68335825-C-T
• rs2306022
• NM_001004439.2:c.1297G>A

Variant summary

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

The NM_001004439.2(ITGA11):​c.1297G>A​(p.Val433Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,612,980 control chromosomes in the GnomAD database, including 5,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.058 (339 hom., cov: 33)
  • Exomes 𝑓: 0.080 (5000 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 32 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=0.008588225).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.1297G>A	p.Val433Met	missense_variant	Exon 12 of 30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.1090G>A	p.Val364Met	missense_variant	Exon 10 of 28		XP_011519665.1
ITGA11	XM_005254228.4	c.991G>A	p.Val331Met	missense_variant	Exon 10 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.1297G>A	p.Val433Met	missense_variant	Exon 12 of 30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.1297G>A	p.Val433Met	missense_variant	Exon 12 of 30	2		ENSP00000403392.2
ITGA11	ENST00000569346.5	n.276G>A		non_coding_transcript_exon_variant	Exon 1 of 4	4
ITGA11	ENST00000566429.1	n.197-11G>A		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8881 AN: 152212 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0616

GnomAD2 exomes AF: 0.0664 AC: 16351 AN: 246158 AF XY: 0.0679

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0592

Gnomad EAS exome AF: 0.0779

Gnomad FIN exome AF: 0.0855

Gnomad NFE exome AF: 0.0857

Gnomad OTH exome AF: 0.0659

GnomAD4 exome AF: 0.0803 AC: 117314 AN: 1460650 Hom.: 5000 Cov.: 34 AF XY: 0.0796 AC XY: 57841 AN XY: 726526

African (AFR) AF: 0.0128 AC: 427 AN: 33472

American (AMR) AF: 0.0232 AC: 1036 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 1485 AN: 26118

East Asian (EAS) AF: 0.0787 AC: 3123 AN: 39672

South Asian (SAS) AF: 0.0548 AC: 4718 AN: 86052

European-Finnish (FIN) AF: 0.0855 AC: 4547 AN: 53208

Middle Eastern (MID) AF: 0.0378 AC: 218 AN: 5766

European-Non Finnish (NFE) AF: 0.0877 AC: 97496 AN: 1111416

Other (OTH) AF: 0.0707 AC: 4264 AN: 60332

GnomAD4 genome AF: 0.0584 AC: 8889 AN: 152330 Hom.: 339 Cov.: 33 AF XY: 0.0571 AC XY: 4252 AN XY: 74490

African (AFR) AF: 0.0155 AC: 646 AN: 41594

American (AMR) AF: 0.0332 AC: 508 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3472

East Asian (EAS) AF: 0.0794 AC: 411 AN: 5174

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4822

European-Finnish (FIN) AF: 0.0774 AC: 821 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5835 AN: 68022

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0739 Hom.: 1626

Bravo AF: 0.0524

TwinsUK AF: 0.0976 AC: 362

ALSPAC AF: 0.0885 AC: 341

ESP6500AA AF: 0.0157 AC: 66

ESP6500EA AF: 0.0822 AC: 693

ExAC AF: 0.0663 AC: 8024

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		-0.17
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.12
Sift	Benign	0.074	T;T
Sift4G	Benign	0.070	T;T
Polyphen		0.93	.;P
Vest4		0.045
MPC		0.12
ClinPred		0.027	T
GERP RS		3.5
Varity_R		0.047
gMVP		0.35
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2306022; hg19: chr15-68628163; COSMIC: COSV59876402;