rs3816612

Variant names:

• chr15-68358842-A-G
• rs3816612
• NM_001004439.2:c.473-257T>C

Variant summary

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

The NM_001004439.2(ITGA11):​c.473-257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 152,300 control chromosomes in the GnomAD database, including 1,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (1002 hom., cov: 32)
• Consequence: ITGA11 NM_001004439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 2 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.473-257T>C		intron_variant	Intron 5 of 29	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.266-257T>C		intron_variant	Intron 3 of 27		XP_011519665.1
ITGA11	XM_005254228.4	c.167-257T>C		intron_variant	Intron 3 of 27		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.473-257T>C		intron_variant	Intron 5 of 29	1	NM_001004439.2	ENSP00000327290.7

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11760 AN: 152182 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0525

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0775 AC: 11806 AN: 152300 Hom.: 1002 Cov.: 32 AF XY: 0.0753 AC XY: 5606 AN XY: 74480

African (AFR) AF: 0.207 AC: 8599 AN: 41532

American (AMR) AF: 0.0411 AC: 629 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.0175 AC: 91 AN: 5194

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4828

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0282 AC: 1920 AN: 68030

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0695 Hom.: 107

Bravo AF: 0.0833

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs3816612; hg19: chr15-68651180;